The following references were utilized by Prof. Dr. Frederick Carrick for his lecture on the Sensory Systems Module 11. Of interest to learners is the integration of the mesolimbic and substantianigral dominergic activating systems in concert with perception and sensory integration.
Prof. Dr. Carrick's reading requirements for the Sensory Systems Module are DeJong's Neurological Examination, Lippincott-Raven Chapters 5-8

------------------------------------------------------------------------------------------------------------------------------------------------------

1. Alais, D.; van, der Smagt MJ; van, den Berg AV; van, de Grind WA. Local and global factors affecting the coherent motion of gratings presented in multiple apertures.
Vision-Res. 1998 Jun; 38(11): 1581-91; ISSN: 0042-6989.
ENGLAND. Using stimuli composed of two independent gratings viewed through multiple apertures, we investigate a number of parameters affecting the integration of locally ambiguous motions into globally coherent motion. In four experiments, we varied local factors (grating spatial frequency, speed, contrast, duty cycle, orientation) and global factors (degree of similarity and common fate between the gratings, and symmetry in the configuration of the grating pattern) and examined their effects on global motion coherence. Our results, confirming accounts offered by previous investigators, indicate that local competition between motion signals generated by contours (ambiguous) and their line terminations (unambiguous) is important in determining global motion coherence in multiple-aperture stimuli. Our results also indicate that global factors can affect perceived coherence independently of local motion signals, suggesting the involvement of higher-level motion areas and a role for non-motion processes such as those involved in pattern and form perception. Comparing motion coherence with other two-dimensional (2-D) stimuli (plaids) shows that 2-D multiple-aperture stimuli are not analogous and that coherence models derived from plaid stimuli do not account for the data.
3. Arden, G. B.; Wolf, J. E.; Tsang, Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision-Res. 1998 Jun; 38(11):
1723-9; ISSN: 0042-6989.
ENGLAND. The paper reviews evidence that before any change in diabetics' fundi, changes occur to blood flow, ERG and visual functions. In the case of colour vision and contrast sensitivity, the changes are partially reversed by breathing oxygen, and therefore are the result of retinal hypoxia. There are also other evidences that hypoxia is a major factor in the development of diabetic retinopathy (DR). Therefore in diabetics with early retinopathy, but normal photopic vision, functional disturbance might appear in dark adaptation, since in such circumstances, (as shown by Linsenmeier and his colleagues) the already low retinal PO2 markedly decreases. This hypothesis has been tested and results consistent with the hypothesis (and with a number of older reports) have been obtained. The significance of this finding to early DR is discussed, and a mechanism suggested whereby prolonged periods of hypoxia during dark adaptation could generate changes in retinal capillaries. Such periods occur each night, and their elimination in diabetics could be therapeutic.
4. Arden, G. B.; Wolf, J. E.; Tsang, Y. Does dark adaptation exacerbate diabetic retinopathy? Evidence and a linking hypothesis. Vision-Res. 1998 Jun; 38(11):
1723-9; ISSN: 0042-6989.
ENGLAND. The paper reviews evidence that before any change in diabetics' fundi, changes occur to blood flow, ERG and visual functions. In the case of colour vision and contrast sensitivity, the changes are partially reversed by breathing oxygen, and therefore are the result of retinal hypoxia. There are also other evidences that hypoxia is a major factor in the development of diabetic retinopathy (DR). Therefore in diabetics with early retinopathy, but normal photopic vision, functional disturbance might appear in dark adaptation, since in such circumstances, (as shown by Linsenmeier and his colleagues) the already low retinal PO2 markedly decreases. This hypothesis has been tested and results consistent with the hypothesis (and with a number of older reports) have been obtained. The significance of this finding to early DR is discussed, and a mechanism suggested whereby prolonged periods of hypoxia during dark adaptation could generate changes in retinal capillaries. Such periods occur each night, and their elimination in diabetics could be therapeutic.
5. Armstrong, D. G.; Hussain, S. K.; Middleton, J.; Peters, E. J.; Wunderlich, R. P.; Lavery, L. A. Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination? Ostomy-Wound-Manage. 1998
May; 44(5): 70-4, 76; ISSN: 0889-5899.
UNITED-STATES. Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.
6. Armstrong, D. G.; Hussain, S. K.; Middleton, J.; Peters, E. J.; Wunderlich, R. P.; Lavery, L. A. Vibration perception threshold: are multiple sites of testing superior to single site testing on diabetic foot examination? Ostomy-Wound-Manage. 1998
May; 44(5): 70-4, 76; ISSN: 0889-5899.
UNITED-STATES. Vibration perception threshold (VPT) values, measured at different anatomic locations on the foot and ankle, and the time to assess VPT and sensory perception using two difference modalities in 102 diabetic patients were compared. VPT was evaluated at the great toe, fifth metatarsal and ankle. Differences in VPT at these three sites, in addition to differences in duration of testing comparing single site (great toe) to multiple sites, and to standard SWMF testing were assessed. No significant difference in VPT between the great toe and fifth metatarsal was found for patients both with and without loss of protective sensation (LOPS). Mean VPT was significantly higher at the ankle compared with both the great toes and fifth metatarsals. However, the difference between ankle and great toe was not significant between patients with and without LOPS [3.9 +/- 11.2 (12%) vs. 3.0 +/- 10.8 (16%) volts, respectively, p > 0.6]. Testing of one site took approximately half the time of Semmes-Weinstein 10-gram monofilament wire SWMF testing (40.5 +/- 16.9 vs. 22.3 +/- 9.1 seconds, p < 0.01) and less than one third the time of three-site VPT testing (10.5 +/- 26.1 vs. 22.3 +/- 9.1 seconds, p < 0.01). There may not be a significant practical benefit in multiple site VPT testing when compared with single site testing on the great toe alone. The value of multiple site testing is further called into question when one notes that the great toe VPT remains the only site tested for sensitivity and specificity for ulceration.
7. Azzi, M.; Betancur, C.; Sillaber, I.; Spangel, R.; Rostene, W.; Berod, A. Repeated administration of the neurotensin receptor antagonist SR 48692 differentially regulates mesocortical and mesolimbic dopaminergic systems. J-Neurochem. 1998
Sep; 71(3): 1158-67; ISSN: 0022-3042.
UNITED-STATES. The purpose of the present study was to investigate the effects of repeated administration of the neurotensin receptor antagonist, SR 48692, on the activity of the mesocortical and mesolimbic dopaminergic (DA) systems. We showed that daily administration of SR 48692 for 15 days (1 mg/kg i.p.) to Wistar rats increased the expression of tyrosine hydroxylase mRNA and protein in the ventral mesencephalon. Simultaneous in vivo microdialysis in the shell part of the nucleus accumbens (AcbSh) and the medial prefrontal cortex (mPFC) revealed that blockade of neurotensin receptors for 15 days decreased basal extracellular levels of DA (approximately 50%) and its metabolites in the AcbSh, whereas no modification in DA levels was observed in the mPFC. In animals submitted to a forced swimming stress, which preferentially enhanced extracellular DA levels in the mPFC, treatment with SR 48692 failed to affect the stress-induced increase in DA. Moreover, given that glucocorticoids can modulate the activity of mesencephalic DA neurons, we examined the effect of the same SR 48692 treatment on corticosterone levels in dialysates from the AcbSh. We found that repeated SR 48692 did not affect the basal levels of free corticosterone, but significantly reduced the increase induced by forced swimming stress. The present results demonstrate that repeated treatment with SR 48692 modulates selectively the DA mesolimbic system when compared with the mesocortical pathway. These findings suggest that long-term treatment with selective neurotensin receptor antagonists could have potential clinical utility in the treatment of neuropsychiatric disorders associated with hyperactivity of the mesolimbic DA systems or the hypothalamic-pituitary-adrenal axis.. EC 1.14.16.2; 0; 0; 0; 0; 146362-70-1; 50-22-6; 51-61-6.
8. Behrendt, R. P. Underconstrained perception: a theoretical approach to the nature and
function of verbal hallucinations. Compr-Psychiatry. 1998 Jul; 39(4): 236-48;
ISSN: 0010-440X.
UNITED-STATES. We do not see the world as it is. Perception forms a
subjective image of the world in a language that has proven to be adaptive to our
interaction with the external world. Perception is mainly determined by current
needs of the organism and goals of behavior. Sensory processing itself does not
culminate in perception and is not essential for perception, since perception
derives from representations of internal symbols and their features. The current
stimulation of sensory organs does, however, constrain our perception.
Perception might be less constrained by the external world in cases of (1)
increased attention, (2) decreased sensory stimulation, or (3) facilitated formation
of cortical associations between representations of expectations and internal
symbols. Hallucinations are perceptions that are underconstrained by external
sensory stimulation. Verbal hallucinations that allow the patient to infer about his
self-image might constitute the core psychopathology in a subset of
schizophrenia. Commenting and discussing voices might be perceived under the
pressure of increased attention to environmental factors that relate to the patient's
social fears and wishes. Secondarily, delusions about the possession of thoughts
and disorders of self-experience may develop.
9. Behrendt, R. P. Underconstrained perception: a theoretical approach to the nature and
function of verbal hallucinations. Compr-Psychiatry. 1998 Jul; 39(4): 236-48;
ISSN: 0010-440X.
UNITED-STATES. We do not see the world as it is. Perception forms a
subjective image of the world in a language that has proven to be adaptive to our
interaction with the external world. Perception is mainly determined by current
needs of the organism and goals of behavior. Sensory processing itself does not
culminate in perception and is not essential for perception, since perception
derives from representations of internal symbols and their features. The current
stimulation of sensory organs does, however, constrain our perception.
Perception might be less constrained by the external world in cases of (1)
increased attention, (2) decreased sensory stimulation, or (3) facilitated formation
of cortical associations between representations of expectations and internal
symbols. Hallucinations are perceptions that are underconstrained by external
sensory stimulation. Verbal hallucinations that allow the patient to infer about his
self-image might constitute the core psychopathology in a subset of
schizophrenia. Commenting and discussing voices might be perceived under the
pressure of increased attention to environmental factors that relate to the patient's
social fears and wishes. Secondarily, delusions about the possession of thoughts
and disorders of self-experience may develop.
10. Belin, P.; McAdams, S.; Smith, B.; Savel, S.; Thivard, L.; Samson, S.; Samson, Y. The
functional anatomy of sound intensity discrimination. J-Neurosci. 1998 Aug 15;
18(16): 6388-94; ISSN: 0270-6474.
UNITED-STATES. The human neuroanatomical substrate of sound intensity
discrimination was investigated by combining psychoacoustics and functional
neuroimaging. Seven normal subjects were trained to detect deviant sounds
presented with a slightly higher intensity than a standard harmonic sound, using a
Go/No Go paradigm. Individual psychometric curves were carefully assessed
using a three-step psychoacoustic procedure. Subjects were scanned while
passively listening to the standard sound and while discriminating changes in
sound intensity at four different performance levels (d' = 1.5, 2.5, 3.5, and 4.5).
Analysis of regional cerebral blood flow data outlined activation, during the
discrimination conditions, of a right hemispheric frontoparietal network already
reported in other studies of selective or sustained attention to sensory input, and
in which activity appeared inversely proportional to intensity discriminability.
Conversely, a right posterior temporal region included in secondary auditory
cortex was activated during discrimination of sound intensity independently of
performance level. These findings suggest that discrimination of sound intensity
involves two different cortical networks: a supramodal right frontoparietal
network responsible for allocation of sensory attentional resources, and a region
of secondary auditory cortex specifically involved in sensory computation of
sound intensity differences.
11. Belin, P.; McAdams, S.; Smith, B.; Savel, S.; Thivard, L.; Samson, S.; Samson, Y. The
functional anatomy of sound intensity discrimination. J-Neurosci. 1998 Aug 15;
18(16): 6388-94; ISSN: 0270-6474.
UNITED-STATES. The human neuroanatomical substrate of sound intensity
discrimination was investigated by combining psychoacoustics and functional
neuroimaging. Seven normal subjects were trained to detect deviant sounds
presented with a slightly higher intensity than a standard harmonic sound, using a
Go/No Go paradigm. Individual psychometric curves were carefully assessed
using a three-step psychoacoustic procedure. Subjects were scanned while
passively listening to the standard sound and while discriminating changes in
sound intensity at four different performance levels (d' = 1.5, 2.5, 3.5, and 4.5).
Analysis of regional cerebral blood flow data outlined activation, during the
discrimination conditions, of a right hemispheric frontoparietal network already
reported in other studies of selective or sustained attention to sensory input, and
in which activity appeared inversely proportional to intensity discriminability.
Conversely, a right posterior temporal region included in secondary auditory
cortex was activated during discrimination of sound intensity independently of
performance level. These findings suggest that discrimination of sound intensity
involves two different cortical networks: a supramodal right frontoparietal
network responsible for allocation of sensory attentional resources, and a region
of secondary auditory cortex specifically involved in sensory computation of
sound intensity differences.
12. Bezard, E.; Bioulac, B.; Gross, C. E. Glutamatergic compensatory mechanisms in
experimental parkinsonism. Prog-Neuropsychopharmacol-Biol-Psychiatry. 1998
May; 22(4): 609-23; ISSN: 0278-5846.
ENGLAND. 1. Injection cannulae allowing access to the SNc were implanted
bilaterally in four monkeys. Once animals had recovered from the operation, daily
low-dose treatment with MPTP was started. 2. Group I comprised two monkeys
under treatment with MPTP, but still asymptomatic. Group II comprised two
monkeys treated with MPTP and presenting clinical symptoms. 3. Both groups
received daily intracranial injections of kynurenic acid in order to block the
glutamatergic afferents to the SNc. 4. In the first group of asymptomatic
monkeys, kynurenic acid induced parkinsonian motor abnormalities. In the second
group of symptomatic monkeys, it increased the severity of clinical signs. 5.
Glutamatergic inputs to the SNc would therefore appear to be implicated in
compensatory phenomena at different stages of experimental parkinsonism.. 0; 0;
28289-54-5; 492-27-3.
13. Blakemore, S. J.; Rees, G.; Frith, C. D. How do we predict the consequences of our
actions? A functional imaging study. Neuropsychologia. 1998 Jun; 36(6): 521-9;
ISSN: 0028-3932.
ENGLAND. Humans are readily able to distinguish expected and unexpected
sensory events. Whether a single mechanism underlies this ability is unknown.
The most common type of expected sensory events are those generated as a
consequence of self-generated actions. Using H2 15O PET, we studied brain
responses to such predictable sensory events (tones) and to similar unpredictable
events and especially how the processing of predictable sensory events is
modified by the context of a causative self-generated action. Increases in activity
when the tones were unpredictable were seen in the inferior and superior temporal
lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-
generated actions produced activity in a number of motor and premotor areas,
including dorsolateral prefrontal cortex. We observed an interaction between the
predictability of stimuli and self-generated actions in several areas, including the
medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior
colliculus and right inferior temporal cortex. This modulation of activity
associated with stimulus predictability in the context of self-generated actions
implies that these areas may be involved in self-monitoring processes. Detection
of expected stimuli and the detection of the sensory consequences of self-
generated actions appear to be functionally distinct processes, and are carried out
in different cortical areas. These observations support theoretical approaches to
cognition that postulate the existence of a self-monitoring system.. 0; 7732-18-5.
14. Blakemore, S. J.; Rees, G.; Frith, C. D. How do we predict the consequences of our
actions? A functional imaging study. Neuropsychologia. 1998 Jun; 36(6): 521-9;
ISSN: 0028-3932.
ENGLAND. Humans are readily able to distinguish expected and unexpected
sensory events. Whether a single mechanism underlies this ability is unknown.
The most common type of expected sensory events are those generated as a
consequence of self-generated actions. Using H2 15O PET, we studied brain
responses to such predictable sensory events (tones) and to similar unpredictable
events and especially how the processing of predictable sensory events is
modified by the context of a causative self-generated action. Increases in activity
when the tones were unpredictable were seen in the inferior and superior temporal
lobe bilaterally, the right parahippocampal gyrus and right parietal cortex. Self-
generated actions produced activity in a number of motor and premotor areas,
including dorsolateral prefrontal cortex. We observed an interaction between the
predictability of stimuli and self-generated actions in several areas, including the
medial posterior cingulate cortex, left insula, dorsomedial thalamus, superior
colliculus and right inferior temporal cortex. This modulation of activity
associated with stimulus predictability in the context of self-generated actions
implies that these areas may be involved in self-monitoring processes. Detection
of expected stimuli and the detection of the sensory consequences of self-
generated actions appear to be functionally distinct processes, and are carried out
in different cortical areas. These observations support theoretical approaches to
cognition that postulate the existence of a self-monitoring system.. 0; 7732-18-5.
15. Bonci, A.; Grillner, P.; Mercuri, N. B.; Bernardi, G. L-Type calcium channels mediate
a slow excitatory synaptic transmission in rat midbrain dopaminergic neurons. J-
Neurosci. 1998 Sep 1; 18(17): 6693-703; ISSN: 0270-6474.
UNITED-STATES. Patch pipettes were used to record whole-cell synaptic
currents under voltage-clamp in dopaminergic neurons in slices of rat substantia
nigra pars compacta and ventral tegmental area. We report that dihydropyridines
(DHPs), L-type Ca2+ channel antagonists, depressed a slow EPSC (EPSCslow)
evoked by a train of focally delivered electrical stimuli. In fact, the amplitude of
the EPSCslow was reduced by the DHP antagonists nifedipine (1-100 microM),
nimodipine (1-100 microM), and isradipine (30 nM-100 microM) in a
concentration-dependent and reversible manner. On the other hand, Bay-K 8644
(1 microM), an L-type Ca2+ channel agonist, increased the EPSCslow. The DHPs
depressed the EPSCslow only when the high-frequency stimulation that was used
to evoke this synaptic current lasted >70 msec. On the other hand, Bay-K 8644
increased the amplitude of the EPSCslow only when it was evoked by a train <70
msec. Moreover, the DHPs did not affect the EPSCfast, the IPSCfast, and the
IPSCslow. The inhibition of the EPSCslow caused by the DHPs is attributed to
presynaptic mechanisms because (1) the inward current generated by exogenously
administered glutamate was not affected and (2) the EPSCslow was reduced to a
similar degree even when the activation state of postsynaptic L-type Ca2+
channels was changed by holding the neurons at -100, -60, and +30 mV. Finally, a
DHP-sensitive component of the EPSCslow could even be detected after the
blockade of N-, Q-, and P-type Ca2+ channels by the combination of omega-
conotoxin GVIA, omega-agatoxin IVA, and omega-conotoxin MVIIC. Taken
together, these results indicate that under certain patterns of synaptic activity, L-
type Ca2+ channels regulate the synaptic release of excitatory amino acids on the
dopaminergic neurons of the ventral mesencephalon.. 0; 0; 0; 51-61-6; 71145-03-
4.
16. Bosworth, C. F.; Sample, P. A.; Gupta, N.; Bathija, R.; Weinreb, R. N. Motion
automated perimetry identifies early glaucomatous field defects. Arch-
Ophthalmol. 1998 Sep; 116(9): 1153-8; ISSN: 0003-9950.
UNITED-STATES. OBJECTIVE: To determine if motion automated perimetry
can identify early glaucomatous visual field defects in patients with suspected
glaucoma (by disc), those with ocular hypertension, and those with primary
open-angle glaucoma. METHODS: Motion automated perimetry, a foveally
centered motion test, and standard visual field tests were conducted on one
randomly selected eye of normal patients (n = 38), patients with suspected
glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and
patients with primary open-angle glaucoma (n = 21). Subjects' performance on
both motion tests were compared with their performance on standard perimetry.
RESULTS: Perimetric motion thresholds significantly distinguished the groups
(P< or =.001), while the foveally centered motion test was unable to separate
them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of
those with suspected glaucoma, 27.8% of those with ocular hypertension, and
5.3% of the normal subjects had abnormal results on motion automated perimetry
testing. Perimetric motion thresholds were significantly correlated with standard
visual field thresholds (P< or =.001). CONCLUSION: Motion automated
perimetry identifies visual field defects in patients who already show standard
visual field loss as well as in a moderate percentage of those with suspected
glaucoma and ocular hypertension, indicating that the testing of discrete locations
might be necessary for increased diagnostic utility.
17. Bosworth, C. F.; Sample, P. A.; Gupta, N.; Bathija, R.; Weinreb, R. N. Motion
automated perimetry identifies early glaucomatous field defects. Arch-
Ophthalmol. 1998 Sep; 116(9): 1153-8; ISSN: 0003-9950.
UNITED-STATES. OBJECTIVE: To determine if motion automated perimetry
can identify early glaucomatous visual field defects in patients with suspected
glaucoma (by disc), those with ocular hypertension, and those with primary
open-angle glaucoma. METHODS: Motion automated perimetry, a foveally
centered motion test, and standard visual field tests were conducted on one
randomly selected eye of normal patients (n = 38), patients with suspected
glaucoma (by disc) (n = 28), patients with ocular hypertension (n = 18), and
patients with primary open-angle glaucoma (n = 21). Subjects' performance on
both motion tests were compared with their performance on standard perimetry.
RESULTS: Perimetric motion thresholds significantly distinguished the groups
(P< or =.001), while the foveally centered motion test was unable to separate
them (P< or =.32). Of the total patients, 90.5% of those with glaucoma, 39.3% of
those with suspected glaucoma, 27.8% of those with ocular hypertension, and
5.3% of the normal subjects had abnormal results on motion automated perimetry
testing. Perimetric motion thresholds were significantly correlated with standard
visual field thresholds (P< or =.001). CONCLUSION: Motion automated
perimetry identifies visual field defects in patients who already show standard
visual field loss as well as in a moderate percentage of those with suspected
glaucoma and ocular hypertension, indicating that the testing of discrete locations
might be necessary for increased diagnostic utility.
18. Bowyer, J. F.; Frame, L. T.; Clausing, P.; Nagamoto Combs, K.; Osterhout, C. A.;
Sterling, C. R.; Tank, A. W. Long-term effects of amphetamine neurotoxicity on
tyrosine hydroxylase mRNA and protein in aged rats. J-Pharmacol-Exp-Ther.
1998 Aug; 286(2): 1074-85; ISSN: 0022-3565.
UNITED-STATES. Four injections (intraperitoneal) of 3 mg/kg amphetamine (2
hr apart) produced pronounced hyperthermia and sustained decreases in
dopamine levels and tyrosine hydroxylase (TH) protein levels in the striatum of
15-month-old male rats. A partial recovery of striatal dopamine levels was
observed at 4 months after amphetamine. In contrast, TH mRNA and TH protein
levels in the midbrain were unaffected at all time points tested up to 4 months
after amphetamine treatment. The number of TH-immunopositive cells in the
midbrain was also unchanged at 4 months after amphetamine, even though the
number of TH-positive axons in the striatum remained dramatically decreased at
this time point. Interestingly, TH-immunopositive cell bodies were observed 4
months after amphetamine in the lateral caudate/putamen, defined anteriorly by
the genu of the corpus collosum and posteriorly by the junction of the anterior
commissures; these striatal TH-positive cells were not observed in saline- or
amphetamine-treated rats that did not become hyperthermic. In addition, low
levels (orders of magnitude lower than that present in the midbrain) of TH mRNA
were detected using reverse transcription-polymerase chain reaction in the
striatum of these amphetamine-treated rats. Our results suggest that even though
there is a partial recovery of striatal dopamine levels, which occurs within 4
months after amphetamine treatment, this recovery is not associated with
increased TH gene expression in the midbrain. Furthermore, new TH-positive
cells are generated in the striatum at this 4-month time point.. EC 1.14.16.2; EC
1.2.1.9; 0; 0; 300-62-9; 51-61-6.
19. Brandt, T.; Bartenstein, P.; Janek, A.; Dieterich, M. Reciprocal inhibitory visual-
vestibular interaction. Visual motion stimulation deactivates the parieto-insular
vestibular cortex. Brain. 1998 Sep; 121( Pt 9): 1749-58; ISSN: 0006-8950.
ENGLAND. The vestibular system--a sensor of head accelerations--cannot
detect self-motion at constant velocity and thus requires supplementary visual
information. The perception of self-motion during constant velocity movement is
completely dependent on visually induced vection. This can be linear vection or
circular vection (CV). CV is induced by large-field visual motion stimulation
during which the stationary subject perceives the moving surroundings as being
stable and himself as being moved. To determine the unknown cortical visual-
vestibular interaction during CV, we conducted a PET activation study on CV in
10 human volunteers. The PET images of cortical areas activated during visual
motion stimulation without CV were compared with those with CV. Hitherto, CV
was explained neurophysiologically by visual-vestibular convergence with
activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV
were mediated by the vestibular cortex, one would expect that an adequate visual
motion stimulus would activate both the visual and vestibular cortex. Contrary to
this expectation, it was shown for the first time that visual motion stimulation
with CV not only activates a medial parieto-occipital visual area bilaterally,
separate from middle temporal/medial superior temporal areas, it also
simultaneously deactivates the parieto-insular vestibular cortex. There was a
positive correlation between the perceived intensity of CV and relative changes in
regional CBF in parietal and occipital areas. These findings support a new
functional interpretation: reciprocal inhibitory visual-vestibular interaction as a
multisensory mechanism for self-motion perception. Inhibitory visual-vestibular
interaction might protect visual perception of self-motion from potential
vestibular mismatches caused by involuntary head accelerations during
locomotion, and this would allow the dominant sensorial weight during self-
motion perception to shift from one sensory modality to the other.
20. Brandt, T.; Bartenstein, P.; Janek, A.; Dieterich, M. Reciprocal inhibitory visual-
vestibular interaction. Visual motion stimulation deactivates the parieto-insular
vestibular cortex. Brain. 1998 Sep; 121( Pt 9): 1749-58; ISSN: 0006-8950.
ENGLAND. The vestibular system--a sensor of head accelerations--cannot
detect self-motion at constant velocity and thus requires supplementary visual
information. The perception of self-motion during constant velocity movement is
completely dependent on visually induced vection. This can be linear vection or
circular vection (CV). CV is induced by large-field visual motion stimulation
during which the stationary subject perceives the moving surroundings as being
stable and himself as being moved. To determine the unknown cortical visual-
vestibular interaction during CV, we conducted a PET activation study on CV in
10 human volunteers. The PET images of cortical areas activated during visual
motion stimulation without CV were compared with those with CV. Hitherto, CV
was explained neurophysiologically by visual-vestibular convergence with
activation of the vestibular nuclei, thalamic subnuclei and vestibular cortex. If CV
were mediated by the vestibular cortex, one would expect that an adequate visual
motion stimulus would activate both the visual and vestibular cortex. Contrary to
this expectation, it was shown for the first time that visual motion stimulation
with CV not only activates a medial parieto-occipital visual area bilaterally,
separate from middle temporal/medial superior temporal areas, it also
simultaneously deactivates the parieto-insular vestibular cortex. There was a
positive correlation between the perceived intensity of CV and relative changes in
regional CBF in parietal and occipital areas. These findings support a new
functional interpretation: reciprocal inhibitory visual-vestibular interaction as a
multisensory mechanism for self-motion perception. Inhibitory visual-vestibular
interaction might protect visual perception of self-motion from potential
vestibular mismatches caused by involuntary head accelerations during
locomotion, and this would allow the dominant sensorial weight during self-
motion perception to shift from one sensory modality to the other.
21. Britten, K. H. Clustering of response selectivity in the medial superior temporal area
of extrastriate cortex in the macaque monkey. Vis-Neurosci. 1998 May; 15(3):
553-8; ISSN: 0952-5238.
ENGLAND. Ever since being described by Mountcastle (Mountcastle, 1957),
columnar organization of sensory cortical areas has provided key leverage into
understanding the functional organization of neocortex. Columnar or clustered
organization of neurons sharing like properties is now known to be widespread,
and probably universal in primary sensory areas. Visual cortex in primates
consists of a primary area and a large number of secondary areas, which are
organized in a manner both hierarchical and parallel (Felleman & Van Essen, 1991;
Young, 1993; Young et al., 1995). One major component in the organization of
extrastriate visual cortex appears to be the division into dorsal and ventral
"streams" of processing (Ungerleider & Mishkin, 1982), each of which is
organized hierarchically. Within each, columnar organization exists at early stages,
but becomes less clear at higher levels. Columnar organization has been described
at the highest level of the ventral stream, inferotemporal cortex (IT, Saleem et al.,
1993; Fujita & Fujita, 1996; Tanaka, 1996), but has not been well characterized at
the higher levels of the dorsal stream. Hints of such organization are found in the
literature (Saito et al., 1986; Lagae et al., 1994), but systematic measurements are
needed. In this paper, I report the existence of clustered organization in the medial
superior temporal area (MST) of the dorsal stream, which is arguably the highest
dominantly visual area on this pathway. I have measured the selectivity of both
single- and multiple-unit activity along oblique electrode penetrations through this
area to three different kinds of optic flow stimuli, and find that nearby neurons are
more similar in their tuning than are more distant ones. This observation
documents the existence of some form of clustered organization and supports the
importance of this area in the processing of optic flow information.
22. Britten, K. H. Clustering of response selectivity in the medial superior temporal area
of extrastriate cortex in the macaque monkey. Vis-Neurosci. 1998 May; 15(3):
553-8; ISSN: 0952-5238.
ENGLAND. Ever since being described by Mountcastle (Mountcastle, 1957),
columnar organization of sensory cortical areas has provided key leverage into
understanding the functional organization of neocortex. Columnar or clustered
organization of neurons sharing like properties is now known to be widespread,
and probably universal in primary sensory areas. Visual cortex in primates
consists of a primary area and a large number of secondary areas, which are
organized in a manner both hierarchical and parallel (Felleman & Van Essen, 1991;
Young, 1993; Young et al., 1995). One major component in the organization of
extrastriate visual cortex appears to be the division into dorsal and ventral
"streams" of processing (Ungerleider & Mishkin, 1982), each of which is
organized hierarchically. Within each, columnar organization exists at early stages,
but becomes less clear at higher levels. Columnar organization has been described
at the highest level of the ventral stream, inferotemporal cortex (IT, Saleem et al.,
1993; Fujita & Fujita, 1996; Tanaka, 1996), but has not been well characterized at
the higher levels of the dorsal stream. Hints of such organization are found in the
literature (Saito et al., 1986; Lagae et al., 1994), but systematic measurements are
needed. In this paper, I report the existence of clustered organization in the medial
superior temporal area (MST) of the dorsal stream, which is arguably the highest
dominantly visual area on this pathway. I have measured the selectivity of both
single- and multiple-unit activity along oblique electrode penetrations through this
area to three different kinds of optic flow stimuli, and find that nearby neurons are
more similar in their tuning than are more distant ones. This observation
documents the existence of some form of clustered organization and supports the
importance of this area in the processing of optic flow information.
23. Britten, K. H.; Newsome, W. T. Tuning bandwidths for near-threshold stimuli in area
MT. J-Neurophysiol. 1998 Aug; 80(2): 762-70; ISSN: 0022-3077.
UNITED-STATES. It is not known whether psychophysical performance
depends primarily on small numbers of neurons optimally tuned to specific visual
stimuli, or on larger populations of neurons that vary widely in their properties.
Tuning bandwidths of single cells can provide important insight into this issue,
yet most bandwidth measurements have been made using suprathreshold visual
stimuli, whereas psychophysical measurements are frequently obtained near
threshold. We therefore examined the directional tuning of cells in the middle
temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we
have employed extensively in combined psychophysical and physiological
studies. The strength of the motion signal (coherence) in these displays can be
varied independently of its direction. For each MT neuron, we characterized the
directional bandwidth by fitting Gaussian functions to directional tuning data
obtained at each of several motion coherences. Directional bandwidth increased
modestly as the coherence of the stimulus was reduced. We then assessed the
ability of MT neurons to discriminate opposed directions of motion along six
equally spaced axes of motion spanning 180 degrees. A signal detection analysis
yielded neurometric functions for each axis of motion, from which neural
thresholds could be extracted. Neural thresholds remained surprisingly low as the
axis of motion diverged from the neuron's preferred-null axis, forming a plateau of
high to medium sensitivity that extended approximately 45 degrees on either side
of the preferred-null axis. We conclude that directional tuning remains broad in
MT when motion signals are reduced to near-threshold values. Thus directional
information is widely distributed in MT, even near the limits of psychophysical
performance. These observations support models in which relatively large
numbers of signals are pooled to inform psychophysical decisions.
24. Britten, K. H.; Newsome, W. T. Tuning bandwidths for near-threshold stimuli in area
MT. J-Neurophysiol. 1998 Aug; 80(2): 762-70; ISSN: 0022-3077.
UNITED-STATES. It is not known whether psychophysical performance
depends primarily on small numbers of neurons optimally tuned to specific visual
stimuli, or on larger populations of neurons that vary widely in their properties.
Tuning bandwidths of single cells can provide important insight into this issue,
yet most bandwidth measurements have been made using suprathreshold visual
stimuli, whereas psychophysical measurements are frequently obtained near
threshold. We therefore examined the directional tuning of cells in the middle
temporal area (MT, or V5) using perithreshold, stochastic motion stimuli that we
have employed extensively in combined psychophysical and physiological
studies. The strength of the motion signal (coherence) in these displays can be
varied independently of its direction. For each MT neuron, we characterized the
directional bandwidth by fitting Gaussian functions to directional tuning data
obtained at each of several motion coherences. Directional bandwidth increased
modestly as the coherence of the stimulus was reduced. We then assessed the
ability of MT neurons to discriminate opposed directions of motion along six
equally spaced axes of motion spanning 180 degrees. A signal detection analysis
yielded neurometric functions for each axis of motion, from which neural
thresholds could be extracted. Neural thresholds remained surprisingly low as the
axis of motion diverged from the neuron's preferred-null axis, forming a plateau of
high to medium sensitivity that extended approximately 45 degrees on either side
of the preferred-null axis. We conclude that directional tuning remains broad in
MT when motion signals are reduced to near-threshold values. Thus directional
information is widely distributed in MT, even near the limits of psychophysical
performance. These observations support models in which relatively large
numbers of signals are pooled to inform psychophysical decisions.
25. Burke, R. E.; Kholodilov, N. G. Programmed cell death: does it play a role in
Parkinson's disease? Ann-Neurol. 1998 Sep; 44(3 Suppl 1): S126-33; ISSN: 0364-
5134.
UNITED-STATES. In recent years, the possibility that programmed cell death
(PCD), which is mediated by genetic programs intrinsic to the cell, may underlie
the degeneration of neurons that occurs in Parkinson's disease (PD) and allied
disorders has become an important hypothesis. Although PCD was originally
identified in tissues as a normal developmental phenomenon, there is no question
that it can also occur in neurologic disease and models thereof. The possibility
that PCD could occur in dopamine neurons in degenerative disease is made
plausible by the observations that natural cell death, with the morphology of
apoptosis, does occur in these neurons and that this event is regulated by
developmental target interactions. In addition, it has been shown that apoptotic
death can be induced in these neurons in some animal models of parkinsonism. We
have shown, for example, that apoptosis can be induced during development by
intrastriatal injection of the neurotoxin 6-hydroxydopamine. Other investigators
have shown that apoptosis can be induced in a chronic model of 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyride toxicity. However, investigations in human PD
brains have yielded mixed results thus far, with some investigators identifying
evidence of apoptotic death but others not. Further investigation of human
postmortem tissue will benefit from a more complete understanding of the
molecular basis of PCD in dopamine neurons, such that its molecular features can
be investigated, rather than strictly relying on the morphologic markers presently
available.. 51-61-6.
26. Carpenter, M. G.; Bellos, A.; Patla, A. E. Is backward stepping over obstacles
achieved through a simple temporal reversal of forward stepping? Int-J-Neurosci.
1998 Apr; 93(3-4): 189-96; ISSN: 0020-7454.
ENGLAND. The main purpose of the study was to examine whether backward
stepping over obstacles was a simple temporal reversal of kinematic and muscle
activation patterns found in forward obstacle avoidance. Obstacle avoidance was
used as a probe to represent one aspect of walking over variable terrain.
Kinematics, trajectories and muscle activation profiles for forward versus
backward stepping over obstacles revealed that the simple reversal of locomotor
patterns observed for level walking cannot be applied to obstacle avoidance.
However, key kinematic data and limb trajectories for backward leading limb
stepping were found to be similar to existing forward trailing limb data. Therefore,
it appears that stepping over obstacles requires a complex upper level
reorganization of the basic locomotor pattern based on biomechanical and sensory
feedback.
27. Carpenter, M. G.; Bellos, A.; Patla, A. E. Is backward stepping over obstacles
achieved through a simple temporal reversal of forward stepping? Int-J-Neurosci.
1998 Apr; 93(3-4): 189-96; ISSN: 0020-7454.
ENGLAND. The main purpose of the study was to examine whether backward
stepping over obstacles was a simple temporal reversal of kinematic and muscle
activation patterns found in forward obstacle avoidance. Obstacle avoidance was
used as a probe to represent one aspect of walking over variable terrain.
Kinematics, trajectories and muscle activation profiles for forward versus
backward stepping over obstacles revealed that the simple reversal of locomotor
patterns observed for level walking cannot be applied to obstacle avoidance.
However, key kinematic data and limb trajectories for backward leading limb
stepping were found to be similar to existing forward trailing limb data. Therefore,
it appears that stepping over obstacles requires a complex upper level
reorganization of the basic locomotor pattern based on biomechanical and sensory
feedback.
28. Cases, O.; Lebrand, C.; Giros, B.; Vitalis, T.; De Maeyer, E.; Caron, M. G.; Price, D.
J.; Gaspar, P.; Seif, I. Plasma membrane transporters of serotonin, dopamine, and
norepinephrine mediate serotonin accumulation in atypical locations in the
developing brain of monoamine oxidase A knock-outs. J-Neurosci. 1998 Sep 1;
18(17): 6914-27; ISSN: 0270-6474.
UNITED-STATES. Genetic loss or pharmacological inhibition of monoamine
oxidase A (MAOA) in mice leads to a large increase in whole-brain levels of
serotonin (5-HT). Excess 5-HT in mouse neonates prevents the normal barrel-like
clustering of thalamic axons in the somatosensory cortex. Projection fields of other
neuron populations may develop abnormally. In the present study, we have
analyzed the localization of 5-HT immunolabeling in the developing brain of
MAOA knock-out mice. We show numerous atypical locations of 5-HT during
embryonic and postnatal development. Catecholaminergic cells of the substantia
nigra, ventral tegmental area, hypothalamus, and locus ceruleus display transient
5-HT immunoreactivity. Pharmacological treatments inhibiting specific
monoamine plasma membrane transporters and genetic crosses with mice lacking
the dopamine plasma membrane transporter show that the accumulation of 5-HT
in these catecholaminergic cells is attributable to 5-HT uptake via the dopamine or
the norepinephrine plasma membrane transporter. In the telencephalon, transient
5-HT immunolabeling is observed in neurons in the CA1 and CA3 fields of the
hippocampus, the central amygdala, the indusium griseum, and the deep layers of
the anterior cingulate and retrosplenial cortices. In the diencephalon, primary
sensory nuclei, as well as the mediodorsal, centrolateral, oval paracentral,
submedial, posterior, and lateral posterior thalamic nuclei, are transiently 5-HT
immunolabeled. The cortical projections of these thalamic nuclei are also labeled.
In the brainstem, neurons in the lateral superior olivary nucleus and the
anteroventral cochlear nucleus are transiently 5-HT immunolabeled. None of these
structures appear to express the monoamine biosynthetic enzyme L-aromatic
amino acid decarboxylase. The administration of monoamine plasma membrane
transporter inhibitors indicates that the 5-HT immunolabeling in these structures
is attributable to an uptake of 5-HT by the 5-HT plasma membrane transporter.
This points to neuron populations that form highly precise projection maps that
could be affected by 5-HT during specific developmental stages.. EC 1.4.3.4; 0; 0;
0; 0; 0; 136253-20-8; 50-67-9; 51-41-2; 51-61-6.
29. Chan, P. K.; Leung, C. K.; Yung, W. H. Differential expression of pre- and
postsynaptic GABA(B) receptors in rat substantia nigra pars reticulata neurones.
Eur-J-Pharmacol. 1998 May 22; 349(2-3): 187-97; ISSN: 0014-2999.
NETHERLANDS. Whole-cell recordings were made from substantia nigra pars
reticulata in rat midbrain slices to study the functional expression of pre- and
postsynaptic GABA(B) receptors in GABA output neurones. Baclofen (up to
300 microM) dose-dependently activated a weak current which was insensitive to
tetrodotoxin and Ca2+-free solution but blocked by Ba2+ and 2-OH-saclofen. The
maximum current activated by baclofen (30 microM) was 43.0 +/- 4.5 pA (n =
27), representing only 23% of that in dopamine neurones. Baclofen (1-30
microM) also reduced the frequency of the GABA(A) receptor-mediated
miniature inhibitory postsynaptic currents while the distribution of their
amplitudes was unaffected. This presynaptic effect of baclofen, prominent at a
concentration as low as 1 microM, was sensitive to 2-OH-saclofen and occluded
by Cd2+, but was unaffected by Ba2+. The results suggest a predominant role of
the presynaptic GABA(B) receptors in substantia nigra pars reticulata. The
relative abundance of pre- and postsynaptic GABA(B) receptor subtypes in this
brain region may also be important in mediating the anticonvulsant effect of
baclofen in rats.. 0; 0; 0; 1134-47-0.
30. Charvet, I.; Hemming, F. J.; Feuerstein, C.; Saxod, R. Mosaic distribution of
chondroitin and keratan sulphate in the developing rat striatum: possible
involvement of proteoglycans in the organization of the nigrostriatal system.
Brain-Res-Dev-Brain-Res. 1998 Aug 8; 109(2): 229-44; ISSN: 0165-3806.
NETHERLANDS. The striatum of the mammalian basal ganglia is composed of
two neurochemically distinct compartments termed patches and matrix that
contribute overall to a mosaic organization. Glycosaminoglycans (GAGs), the
sugar moieties of proteoglycans, provide specific spatio-temporal guidance cues
during the development of several functional neural systems. However, their
distribution within the nigrostriatal system has not been investigated yet. Here,
the immunohistochemical distributions of unsulphated (C0S), 4-sulphated (C4S)
and 6-sulphated chondroitin (C6S) and keratan sulphate (KS) were examined in
the developing neostriatum of rat and compared with the distribution of
dopaminergic terminals. All the chondroitin sulphate (CS) isomers are
homogeneously expressed in the embryonic striatum. After birth, C0S and C6S
reveal the striatal mosaic in being preferentially expressed within the matrix
compartment and in boundaries around patches whereas the C4S epitope is
present in both compartments, with a slight patchy distribution. KS expression is
detected first in the patches during the early postnatal period and subsequently
only in the matrix compartment. All these GAG expressions disappear as the
brain matures except for C4S which remains high throughout adult life.
Furthermore, studies within the developing medial forebrain bundle reveal that CS
isomers, but not KS, are expressed in and around the dopamine axonal tract but
show similar developmental patterns of distribution which do not appear to be
specifically associated with the nigrostriatal pathway. These results suggest a
possible implication of proteoglycans during the development of the striatum and
may be useful for understanding the complex cellular and molecular interactions in
degeneration and plasticity of the nigrostriatal circuit in Parkinson's disease.
Copyright 1998 Elsevier Science B.V.. 0; 0; 0; 9007-27-6; 9056-36-4.
31. Cropper, S. J. Detection of chromatic and luminance contrast modulation by the
visual system. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 1969-86;
ISSN: 1084-7529.
UNITED-STATES. The data presented in this paper examine the ability of
observers to detect a modulation in the contrast of chromatic and luminance
gratings as a function of the carrier contrast, duration, and spatial frequency. The
nature of the signal underlying this ability is investigated by examining both the
paradigm used to make the measurement and the effect of grating masks on
performance in the tasks. The results show that observers' ability to discriminate
amplitude modulation from an unmodulated carrier is dependent on carrier
contrast but only up to approximately 5-8 times carrier-detection threshold.
Discrimination is, however, independent of spatial frequency [10-1 cycles per
degree (cpd) component-frequency range], carrier color, and, most surprisingly,
stimulus duration (1000-30 ms). This set of experiments compliments data from
previous papers and assimilates many of the conclusions drawn from this
previous data. There is absolutely no evidence for the existence of a distortion
product mediating performance under any of the current conditions, and the data
seriously question whether the visual system might use such a signal even if it
does exist under more extreme conditions than those used here. The evidence
suggests that the visual system detects variations in both chromatic and luminance
contrast by means of a mechanism operating locally upon the spatial structure of
the carrier.
32. Cropper, S. J. Detection of chromatic and luminance contrast modulation by the
visual system. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 1969-86;
ISSN: 1084-7529.
UNITED-STATES. The data presented in this paper examine the ability of
observers to detect a modulation in the contrast of chromatic and luminance
gratings as a function of the carrier contrast, duration, and spatial frequency. The
nature of the signal underlying this ability is investigated by examining both the
paradigm used to make the measurement and the effect of grating masks on
performance in the tasks. The results show that observers' ability to discriminate
amplitude modulation from an unmodulated carrier is dependent on carrier
contrast but only up to approximately 5-8 times carrier-detection threshold.
Discrimination is, however, independent of spatial frequency [10-1 cycles per
degree (cpd) component-frequency range], carrier color, and, most surprisingly,
stimulus duration (1000-30 ms). This set of experiments compliments data from
previous papers and assimilates many of the conclusions drawn from this
previous data. There is absolutely no evidence for the existence of a distortion
product mediating performance under any of the current conditions, and the data
seriously question whether the visual system might use such a signal even if it
does exist under more extreme conditions than those used here. The evidence
suggests that the visual system detects variations in both chromatic and luminance
contrast by means of a mechanism operating locally upon the spatial structure of
the carrier.
33. Dai, M.; Tepper, J. M. Do silent dopaminergic neurons exist in rat substantia nigra in
vivo? Neuroscience. 1998 Aug; 85(4): 1089-99; ISSN: 0306-4522.
UNITED-STATES. A subpopulation of inactive or "silent" dopaminergic
neurons has been reported to exist in vivo in rat substantia nigra, comprising up to
50% of nigral dopaminergic neurons. The existence of this large proportion of
silent neurons has been inferred from various experimental manipulations, but
never demonstrated directly. In the present study, striatal or medial forebrain
bundle stimulation was used to activate antidromically substantia nigra
dopaminergic neurons in vivo. Antidromic spikes of dopaminergic neurons
observed by extracellular single-unit recordings in the absence of spontaneous
activity were employed as indicators of the presence of a silent cell. A total of
312 dopamine neurons were recorded, including 190 neurons that could be
antidromically activated from the striatum and/or the medial forebrain bundle. All
neurons exhibited spontaneous activity. The firing rates were unimodally
distributed about the mean of 4 spikes/s, and very few cells were observed to fire
at less than 0.5 spikes/s. The numbers of spontaneously active and antidromically
activated dopaminergic neurons per track were recorded and compared with the
number of antidromically responding silent dopaminergic neurons per track after
systemic apomorphine administration. Under control conditions, 0.80 +/- 0.10 or
1.36 +/- 0.13 spontaneously active neurons per track could be antidromically
activated at 1.0 mA by striatal or medial forebrain bundle stimulation,
respectively. After apomorphine completely suppressed spontaneous activity,
0.69 +/- 0.08 and 1.39 +/- 0.14 antidromic neurons per track were detected by
stimulating the striatum or medial forebrain bundle respectively at 1.0 mA,
demonstrating that silent dopaminergic neurons can be reliably identified through
antidromic activation. In sharp contrast to previous reports, these data suggest
that silent neurons do not comprise a substantial proportion of the total number
of dopaminergic neurons in the substantia nigra. Reverse chi2 analysis revealed
that, if they exist at all, silent dopaminergic neurons make up less than 2% of the
dopaminergic cells in the substantia nigra. These findings are related to current
theories of the mechanisms of action of antipsychotic drugs and the maintenance
of near-normal levels of dopamine in the striatum following large-scale loss of
nigral dopaminergic neurons.. 0; 51-61-6; 58-00-4.
34. Date, I.; Aoi, M.; Tomita, S.; Collins, F.; Ohmoto, T. GDNF administration induces
recovery of the nigrostriatal dopaminergic system both in young and aged
parkinsonian mice. Neuroreport. 1998 Jul 13; 9(10): 2365-9; ISSN: 0959-4965.
ENGLAND. Glial cell line-derived neurotrophic factor (GDNF) is a member of
the transforming growth factor beta superfamily and acts as a neurotrophic factor
for the nigrostriatal dopaminergic system. GDNF was injected stereotaxically into
the striatum of young (2 months old) and aged (12 months old) C57BL/6 mice
that were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) 1
week earlier. Immunocytochemical and neurochemical analyses showed significant
recovery of the nigrostriatal dopaminergic system both in young and in aged mice.
Since Parkinson's disease is a neurodegenerative disorder mainly affecting elderly
people, this result demonstrates the potential usefulness of GDNF in treating
Parkinson's disease.. EC 1.14.16.2; 0; 0; 0; 0; 28289-54-5; 51-61-6.
35. David, V.; Durkin, T. P.; Cazala, P. Rewarding effects elicited by the microinjection
of either AMPA or NMDA glutamatergic antagonists into the ventral tegmental
area revealed by an intracranial self-administration paradigm in mice. Eur-J-
Neurosci. 1998 Apr; 10(4): 1394-402; ISSN: 0953-816X.
FRANCE. In order to study the functional role of the trans-synaptic neuronal
interaction between glutamatergic afferents and mesolimbic dopaminergic neurons
in internal reward processes, BALB/c male mice were unilaterally implanted with
a guide-cannula, the tip of which was positioned 1.5 mm above the ventral
tegmental area (VTA). On each day of the following experimental period, a
stainless steel injection cannula was inserted into the VTA in order to study the
eventual self-administration behaviour of either the competitive N-methyl-D-
aspartate antagonist, D(-)-2-amino-7-phosphonoheptanoic acid (AP-7) or the
alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid antagonist, 6,7-
dinitroquinoxaline-2,3-dione (DNQX) (3 ng/50 nL) using a spatial discrimination
task in a Y maze. Mice rapidly discriminated between the arm enabling a
microinjection of either of these glutamatergic antagonists and the neutral arm of
the maze, and a robust self-administration of either of these compounds was
observed from the first session of acquisition. These data provide strong evidence
that the intra-VTA microinjection of either of these subclasses of glutamatergic
antagonist produces an effect which is interpreted centrally by the experimental
subjects as being highly rewarding. Once the self-administration response had
been fully acquired by the experimental subjects, preinjection of the dopaminergic
D2 antagonist, sulpiride (50 mg/kg i.p.), 30 min before the test, produced a rapid
extinction of the self-administration response. This latter result demonstrates the
dopaminergic D2 receptor dependence of this intra-VTA self-administration of
both of these subclasses of glutamatergic antagonist. We conclude that the
different glutamatergic afferent neuronal inputs to the VTA globally exert, in vivo,
via the mediation of interposed endogenous GABAergic interneurons, a tonic
trans-synaptic inhibitory regulation of neuronal activity in the mesolimbic
dopaminergic pathway and that this complex neuronal interaction in the VTA
plays a significant functional part in the modulation of internal reward processes..
0; 0; 0; 0; 0; 15676-16-1; 2379-57-9; 76726-92-6; 85797-13-3.
36. Demb, J. B.; Boynton, G. M.; Best, M.; Heeger, D. J. Psychophysical evidence for a
magnocellular pathway deficit in dyslexia. Vision-Res. 1998 Jun; 38(11): 1555-9;
ISSN: 0042-6989.
ENGLAND. The relationship between reading ability and psychophysical
performance was examined to test the hypothesis that dyslexia is associated with
a deficit in the magnocellular (M) pathway. Speed discrimination thresholds and
contrast detection thresholds were measured under conditions (low mean
luminance, low spatial frequency, high temporal frequency) for which
psychophysical performance presumably depends on M pathway integrity.
Dyslexic subjects had higher psychophysical thresholds than controls in both the
speed discrimination and contrast detection tasks, but only the differences in
speed thresholds were statistically significant. In addition, there was a strong
correlation between individual differences in speed thresholds and reading rates.
These results support the hypothesis for an M pathway abnormality in dyslexia,
and suggest that motion discrimination may be a more sensitive psychophysical
predictor of dyslexia than contrast sensitivity.
37. Demb, J. B.; Boynton, G. M.; Best, M.; Heeger, D. J. Psychophysical evidence for a
magnocellular pathway deficit in dyslexia. Vision-Res. 1998 Jun; 38(11): 1555-9;
ISSN: 0042-6989.
ENGLAND. The relationship between reading ability and psychophysical
performance was examined to test the hypothesis that dyslexia is associated with
a deficit in the magnocellular (M) pathway. Speed discrimination thresholds and
contrast detection thresholds were measured under conditions (low mean
luminance, low spatial frequency, high temporal frequency) for which
psychophysical performance presumably depends on M pathway integrity.
Dyslexic subjects had higher psychophysical thresholds than controls in both the
speed discrimination and contrast detection tasks, but only the differences in
speed thresholds were statistically significant. In addition, there was a strong
correlation between individual differences in speed thresholds and reading rates.
These results support the hypothesis for an M pathway abnormality in dyslexia,
and suggest that motion discrimination may be a more sensitive psychophysical
predictor of dyslexia than contrast sensitivity.
38. Diana, M.; Melis, M.; Muntoni, A. L.; Gessa, G. L. Mesolimbic dopaminergic decline
after cannabinoid withdrawal. Proc-Natl-Acad-Sci-U-S-A. 1998 Aug 18; 95(17):
10269-73; ISSN: 0027-8424.
UNITED-STATES. The mesolimbic dopamine system has recently been
implicated in the long-term aversive consequences of withdrawal from major drugs
of abuse. In the present study we sought to determine whether mesolimbic
dopamine neurons are involved in the neurobiologic mechanisms underlying
withdrawal from chronic cannabinoid exposure. Rats were treated chronically with
the major psychoactive ingredient of hashish and marijuana, Delta9-
tetrahydrocannabinol (Delta9-THC). Administration of the cannabinoid
antagonist SR 141716A precipitated an intense behavioral withdrawal syndrome,
whereas abrupt Delta9-THC suspension failed to produce overt signs of
abstinence. In contrast, both groups showed a reduction in dopamine cells activity
as indicated by extracellular single unit recordings from antidromically identified
meso-accumbens dopamine neurons. The administration of Delta9-THC to
spontaneously withdrawn rats restored neuronal activity. Conversely, SR
141716A produced a further decrease of spontaneous activity in cannabinoid-
treated although it was ineffective in control rats. These data indicate that
withdrawal from chronic cannabinoid administration is associated with reduced
dopaminergic transmission in the limbic system, similar to that observed with
other addictive drugs; these changes in neuronal plasticity may play a role in drug
craving and relapse into drug addiction.. 1972-08-3; 51-61-6.
39. Drevets, W. C.; Ongur, D.; Price, J. L. Neuroimaging abnormalities in the subgenual
prefrontal cortex: implications for the pathophysiology of familial mood
disorders. Mol-Psychiatry. 1998 May; 3(3): 220-6, 190-1; ISSN: 1359-4184.
ENGLAND. The prefrontal cortex (PFC) ventral to the genu of the corpus
callosum has been implicated in the modulation of visceral responses to stressful
and emotionally provocative stimuli, based upon analysis of lesion effects
involving this area in humans and experimental animals. In a recent magnetic
resonance imaging (MRI) study of familial mood disorders, we demonstrated that
the mean grey matter volume of this cortex is abnormally reduced in subjects with
major depressive disorder (MDD) and bipolar disorder, irrespective of their
treatment status or current mood state. Moreover, in preliminary
histopathological assessments of subgenual PFC tissue taken post mortem from
subjects with MDD and bipolar disorder we obtained results suggesting that this
decrement in grey matter volume is associated with a reduction in glia without an
equivalent loss of neurons. The potential functional significance of these
neuroimaging and microscopic abnormalities is discussed with respect to evidence
that subgenual PFC dysfunction may disturb stress-related autonomic and
neuroendocrine responses and reward-related mesolimbic dopamine function.
These data may thus hold important implications for the development of neural
models of mood disorders that can account for the abnormal hedonic,
motivational, neuroendocrine, and autonomic manifestations evident in these
idiopathic conditions.
40. Driver, J.; Spence, C. Crossmodal attention. Curr-Opin-Neurobiol. 1998 Apr; 8(2):
245-53; ISSN: 0959-4388.
ENGLAND. Most selective attention research has considered only a single
sensory modality at a time, but in the real world, our attention must be
coordinated crossmodally. Recent studies reveal extensive crossmodal links in
attention across the various modalities (i.e. audition, vision, touch and
proprioception). Attention typically shifts to a common location across the
modalities, despite the vast differences in their initial coding of space. These
spatial synergies in attention can be maintained even when receptors are realigned
across the modalities by changes in posture. Some crossmodal integration can arise
preattentively. The mechanisms underlying these crossmodal links can be
examined in a convergent manner by integrating behavioural studies of normal
subjects and brain-damaged patients with neuroimaging and neurophysiological
studies.
41. Driver, J.; Spence, C. Crossmodal attention. Curr-Opin-Neurobiol. 1998 Apr; 8(2):
245-53; ISSN: 0959-4388.
ENGLAND. Most selective attention research has considered only a single
sensory modality at a time, but in the real world, our attention must be
coordinated crossmodally. Recent studies reveal extensive crossmodal links in
attention across the various modalities (i.e. audition, vision, touch and
proprioception). Attention typically shifts to a common location across the
modalities, despite the vast differences in their initial coding of space. These
spatial synergies in attention can be maintained even when receptors are realigned
across the modalities by changes in posture. Some crossmodal integration can arise
preattentively. The mechanisms underlying these crossmodal links can be
examined in a convergent manner by integrating behavioural studies of normal
subjects and brain-damaged patients with neuroimaging and neurophysiological
studies.
42. Dugast, C.; Souliere, F.; Schmitt, P.; Casanovas, J. M.; Fattaccini, C. M.; Mocaer, E.;
Lesourd, M.; Renaud, B.; Artigas, F.; Hamon, M.; Chouvet, G. Is the potent 5-
HT1A receptor agonist, alnespirone (S-20499), affecting dopaminergic systems in
the rat brain? Eur-J-Pharmacol. 1998 Jun 5; 350(2-3): 171-80; ISSN: 0014-2999.
NETHERLANDS. The effects of the new methoxy-chroman 5-HT1A receptor
agonist, alnespirone (S-20499), on the dopamine systems in the rat brain were
assessed in vivo by means of electrophysiological and neurochemical techniques.
Cumulative doses of alnespirone (0.032-4.1 mg kg(-1), i.v.) did not modify the
spontaneous firing rate of dopamine neurons in the substantia nigra as well as in
the ventral tegmental area. The local application of alnespirone (0.1-10 microM)
by reverse microdialysis into the dorsal striatum did not affect the dopamine
output but induced a moderate, although dose-independent, increase of 5-HT (5-
hydroxytryptamine, serotonin) concentrations in the dialysate. As expected of a
5-HT1A receptor agonist, intraperitoneal (i.p.) administration of alnespirone at 2-
32 mg kg(-1) markedly decreased 5-HT turnover in the striatum. Parallel
measurements of dopamine turnover showed that alnespirone exerted no effect
except at the highest dose (32 mg kg(-1), i.p.) for which a significant increase was
observed. Interestingly, both alnespirone-induced reduction in 5-HT turnover and
increase in dopamine turnover could be prevented by pretreatment with the
selective 5-HT1A receptor antagonist WAY-100635 (N-[2-[4-(2-
methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexa ne carboxamide).
Altogether, these data indicate that alnespirone does not exert any direct influence
on central dopamine systems. The enhanced dopamine turnover due to
alnespirone at high dose appeared to result from 5-HT1A receptor stimulation,
further supporting the idea that this receptor type may play a key role in 5-HT-
dopamine interactions in brain.. EC 4.1.1.-; 0; 0; 0; 0; 0; 112692-38-3; 143413-
68-7; 51-61-6; 56-69-9; 63-84-3.
43. Duke, C. C.; Crewther, S. G.; Lawson, M. L.; Henry, L.; Kiely, P. M.; West, S. J.;
Crewther, D. P. Motion perception in global versus local attentional modes. Aust-
N-Z-J-Ophthalmol. 1998 May; 26 Suppl 1: S114-6; ISSN: 0814-9763.
AUSTRALIA. PURPOSE: Global and local attention are two forms of selective
visual attention which activate different areas of the cortex. The purpose of this
experiment was to test subjects' motion coherence thresholds under conditions of
global or local attention. It was hypothesized that thresholds in global attention
would be lower than in local attention. METHODS: Eleven adult subjects
participated in this study. Subjects were required to identify direction of motion
at variable coherence levels, while simultaneously identifying either the global or
local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s).
RESULTS: The results showed that letter identification (global or local) did not
significantly affect motion coherence thresholds; however, thresholds were
significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS:
These results highlight the attentional limitations of visual information shown by
increased motion coherence thresholds when two objects must be identified
simultaneously in a brief display.
44. Duke, C. C.; Crewther, S. G.; Lawson, M. L.; Henry, L.; Kiely, P. M.; West, S. J.;
Crewther, D. P. Motion perception in global versus local attentional modes. Aust-
N-Z-J-Ophthalmol. 1998 May; 26 Suppl 1: S114-6; ISSN: 0814-9763.
AUSTRALIA. PURPOSE: Global and local attention are two forms of selective
visual attention which activate different areas of the cortex. The purpose of this
experiment was to test subjects' motion coherence thresholds under conditions of
global or local attention. It was hypothesized that thresholds in global attention
would be lower than in local attention. METHODS: Eleven adult subjects
participated in this study. Subjects were required to identify direction of motion
at variable coherence levels, while simultaneously identifying either the global or
local letter. Three velocities were used for coherent motion (3, 6 and 18 degrees/s).
RESULTS: The results showed that letter identification (global or local) did not
significantly affect motion coherence thresholds; however, thresholds were
significantly higher at 18 degrees/s than in the lower velocities. CONCLUSIONS:
These results highlight the attentional limitations of visual information shown by
increased motion coherence thresholds when two objects must be identified
simultaneously in a brief display.
45. Edwards, M.; Badcock, D. R.; Smith, A. T. Independent speed-tuned global-motion
systems. Vision-Res. 1998 Jun; 38(11): 1573-80; ISSN: 0042-6989.
ENGLAND. Several experiments were conducted to investigate the role of speed
in global-motion processing; the extraction of the direction of motion of a small
subset of coherently-moving (signal) dots in a stimulus in which the other (noise)
dots move in random directions. The specific aim of the experiments was to
determine whether multiple speed-tuned global-motion systems exist. The results
of these experiments are: (1) when the signal dots were chosen from a group of
dots moving at 1.2 degrees s-1, the speed of additional-noise dots had to be below
4.8 degrees s-1 for them to affect global-motion extraction; (2) the addition of
static dots did not impair the extraction of a global-motion signal carried by dots
moving at 1.2 degrees s-1; (3) noise dots moving at 1.2 degrees s-1 impaired the
extraction of a global-motion signal from dots moving at 10.8 degrees s-1, though
not to the same extent as dots moving at a higher speed; and (4) these results were
dependent upon speed, not spatial-step size or luminance contrast. These results
are interpreted as indicating that global-motion extraction occurs within at least
two independent speed tuned systems. One of these systems is sensitive to high
speeds and the other to low speeds.
46. Edwards, M.; Badcock, D. R.; Smith, A. T. Independent speed-tuned global-motion
systems. Vision-Res. 1998 Jun; 38(11): 1573-80; ISSN: 0042-6989.
ENGLAND. Several experiments were conducted to investigate the role of speed
in global-motion processing; the extraction of the direction of motion of a small
subset of coherently-moving (signal) dots in a stimulus in which the other (noise)
dots move in random directions. The specific aim of the experiments was to
determine whether multiple speed-tuned global-motion systems exist. The results
of these experiments are: (1) when the signal dots were chosen from a group of
dots moving at 1.2 degrees s-1, the speed of additional-noise dots had to be below
4.8 degrees s-1 for them to affect global-motion extraction; (2) the addition of
static dots did not impair the extraction of a global-motion signal carried by dots
moving at 1.2 degrees s-1; (3) noise dots moving at 1.2 degrees s-1 impaired the
extraction of a global-motion signal from dots moving at 10.8 degrees s-1, though
not to the same extent as dots moving at a higher speed; and (4) these results were
dependent upon speed, not spatial-step size or luminance contrast. These results
are interpreted as indicating that global-motion extraction occurs within at least
two independent speed tuned systems. One of these systems is sensitive to high
speeds and the other to low speeds.
47. Erhardt, S.; Andersson, B.; Nissbrandt, H.; Engberg, G. Inhibition of firing rate and
changes in the firing pattern of nigral dopamine neurons by gamma-
hydroxybutyric acid (GHBA) are specifically induced by activation of GABA(B)
receptors. Naunyn-Schmiedebergs-Arch-Pharmacol. 1998 Jun; 357(6): 611-9;
ISSN: 0028-1298.
GERMANY. Previous studies have shown that administration of gamma-
hydroxybutyric acid (GHBA) or the GABA(B) receptor agonist baclofen are
associated with a decrease in firing rate, a regularisation of firing pattern and a
decrease in burst activity of midbrain dopamine (DA) neurons in the substantia
nigra (SN). In the present study we compared the ability of the novel GABA(B)
receptor antagonist SCH 50911 and the selective antagonist of GHBA binding
sites, NCS-382, to antagonise the effects of baclofen or GHBA, respectively, on
the neuronal activity of DA neurons in anaesthetised rats. SCH 50911 (75 mg/kg,
i.v.) was found to antagonise the decrease in firing rate, the regularisation of firing
rhythm and the decrease of burst activity in DA cells, induced by baclofen (1-32
mg/kg, i.v.) or GHBA (12.5-1600 mg/kg, i.v.). NCS-382 (100 mg/kg, i.v.) did not
affect the baclofen-induced changes in neuronal activity. Neither was the drug able
to influence the GHBA-induced alterations in firing rate or in burst activity,
although NCS-382 to some extent antagonised the regularisation of the firing
pattern observed following low doses of GHBA (< or =100 mg/kg). The results of
the present study give further support for the notion that the GHBA-induced
changes in neuronal activity of nigral dopamine neurons are mediated by
stimulation of GABA(B) receptors.. 0; 0; 0; 0; 0; 0; 0; 0; 1134-47-0; 131733-92-
1; 502-85-2; 51-61-6.
48. Figlewicz, D. P.; Patterson, T. A.; Johnson, L. B.; Zavosh, A.; Israel, P. A.; Szot, P.
Dopamine transporter mRNA is increased in the CNS of Zucker fatty (fa/fa) rats.
Brain-Res-Bull. 1998 Jun; 46(3): 199-202; ISSN: 0361-9230.
UNITED-STATES. The obese Zucker fa/fa rat is characterized by
hyperinsulinemia, obesity, and altered monoamine metabolism in the central
nervous system (CNS). It has been proposed that the changes in monoamine
metabolism may contribute to the metabolic pathophysiology of these animals.
Because it has been reported that insulin may regulate the catecholamine reuptake
transporters, which terminate monoaminergic synaptic signaling, in the present
study we tested whether messenger ribonucleic acid (mRNA) levels for the
noradrenergic (NE) or dopaminergic (DA) transporters were altered in obese fa/fa
vs. lean Fa/Fa Zucker rats. We found significantly elevated DA transporter levels
in both the ventral tegmental area/substantia nigra pars compacta (VTA/SNc) and
zona incerta (ZI) of obese Zucker fa/fa rats (164 +/- 24% of control levels, p =
.024; and 316 +/- 61% of control levels, p = .019, respectively). Measurement of
mRNA for tyrosine hydroxylase (TH), the rate-limiting enzyme for NE and DA
synthesis revealed no effect of the fa gene in either NE or DA neurons. These
findings suggest that increased DA clearance, and perhaps decreased DA signaling,
may occur in the obese Zucker fa/fa rat.. EC 1.14.16.2; 0; 0; 0.
49. Fushimi, M.; Niiyama, Y.; Fujiwara, R.; Satoh, N.; Hishikawa, Y. Some sensory
stimuli generate spontaneous K-complexes. Psychiatry-Clin-Neurosci. 1998 Apr;
52(2): 150-2; ISSN: 1323-1316.
AUSTRALIA. The present study was performed in order to determine whether
spontaneous K-complex are induced by sensory stimuli. Electroencephalogram
(EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous
K-complex were separately averaged with respect to the peak of N300, one of the
main components constituting the K-complex. Small negative and positive
components were found immediately before the main components of spontaneous
K-complex in averaged EEG. These two components were judged to correspond
to N100 and P200 induced by the sound stimulus. The present findings suggest
that the spontaneous K-complex is not a spontaneous phenomenon but that it is
induced by sensory stimuli.
50. Fushimi, M.; Niiyama, Y.; Fujiwara, R.; Satoh, N.; Hishikawa, Y. Some sensory
stimuli generate spontaneous K-complexes. Psychiatry-Clin-Neurosci. 1998 Apr;
52(2): 150-2; ISSN: 1323-1316.
AUSTRALIA. The present study was performed in order to determine whether
spontaneous K-complex are induced by sensory stimuli. Electroencephalogram
(EEG) segments in stage 2 sleep containing an evoked K-complex or spontaneous
K-complex were separately averaged with respect to the peak of N300, one of the
main components constituting the K-complex. Small negative and positive
components were found immediately before the main components of spontaneous
K-complex in averaged EEG. These two components were judged to correspond
to N100 and P200 induced by the sound stimulus. The present findings suggest
that the spontaneous K-complex is not a spontaneous phenomenon but that it is
induced by sensory stimuli.
51. Garcia Perez, M. A.; Sierra Vazquez, V. The optimal motion stimulus: comments on
Watson and Turano (1995) [letter]. Vision-Res. 1998 Jun; 38(11): 1611-21; ISSN:
0042-6989.
ENGLAND. Watson and Turano (Vision Research 1995;35:325-336) described
experimental research aimed at determining the motion stimulus that the visual
system detects best. They reported conflicting results in the determination of the
optimal spatial size and they interpreted them as an effect of probability
summation. They also reported disagreement with earlier results of Watson et al.
(Nature 1983;302:419-422). This study shows (i) that probability summation is
not responsible for those results and (ii) that they can be explained as a
consequence of the method that was used to search for the optimal stimulus.
52. Garcia Perez, M. A.; Sierra Vazquez, V. The optimal motion stimulus: comments on
Watson and Turano (1995) [letter]. Vision-Res. 1998 Jun; 38(11): 1611-21; ISSN:
0042-6989.
ENGLAND. Watson and Turano (Vision Research 1995;35:325-336) described
experimental research aimed at determining the motion stimulus that the visual
system detects best. They reported conflicting results in the determination of the
optimal spatial size and they interpreted them as an effect of probability
summation. They also reported disagreement with earlier results of Watson et al.
(Nature 1983;302:419-422). This study shows (i) that probability summation is
not responsible for those results and (ii) that they can be explained as a
consequence of the method that was used to search for the optimal stimulus.
53. Gash, D. M.; Zhang, Z.; Gerhardt, G. Neuroprotective and neurorestorative
properties of GDNF. Ann-Neurol. 1998 Sep; 44(3 Suppl 1): S121-5; ISSN: 0364-
5134.
UNITED-STATES. Glial cell line-derived neurotrophic factor (GDNF) promotes
recovery of the injured nigrostriatal dopamine system and improves motor
functions in both rodent and nonhuman primate models of Parkinson's disease
(PD). The neurorestorative effects of a single administration of GDNF last for at
least 1 month and can be maintained in rhesus monkeys by monthly injections.
Adult midbrain dopamine neurons stimulated by GDNF show increased cell size,
neurite extent, and expression of phenotypic markers. In parkinsonian nonhuman
primates, GDNF treatment improves three of the cardinal features of PD:
bradykinesia, rigidity, and postural instability. Although intracerebral
administration is necessary because of the blood-brain barrier, intraventricular,
intrastriatal, and intranigral routes of administration have been found to be
efficacious in rodents and nonhuman primates. GDNF also induces
neuroprotective changes in dopamine neurons which are active within hours after
trophic factor administration. The powerful neuroprotective and neurorestorative
properties of GDNF seen in preclinical studies suggest that trophic factors may
play an important role in treating PD.. 0; 0; 0; 0; 51-61-6.
54. Gerber, B.; Smith, B. H. Visual modulation of olfactory learning in honeybees. J-Exp-
Biol. 1998 Jul; 201( Pt 14): 2213-7; ISSN: 0022-0949.
ENGLAND. We use classical conditioning of the honeybee (Apis mellifera)
proboscis extension reflex with a visual (A) and an olfactory (X) conditioned
stimulus in a blocking paradigm. Typically, learning about one element (X) of a
compound (AX) is decreased (blocked) if the other component (A) has previously
been rewarded alone. Our results show that visual pretraining did not produce
blocking in honeybees: instead, forward pairings of A with a reward increased
subsequent learning about X relative to a backward pairing control. This finding
violates the independence assumption, which holds that elements of inter-modal
compound stimuli change associative strength independently of each other.
Furthermore, it is at odds with common theories of conditioning that predict
blocking and assume that the elements of a compound stimulus rely on one
common internal reinforcing signal. Taking the functional anatomy of the
honeybee brain into account, we suggest that vision and olfaction may not rely on
the same internal reinforcing signal; compound interactions might thus reflect the
wiring of the honeybee nervous system and the biological significance of different
sensory modalities during natural behaviour.
55. Gerber, B.; Smith, B. H. Visual modulation of olfactory learning in honeybees. J-Exp-
Biol. 1998 Jul; 201( Pt 14): 2213-7; ISSN: 0022-0949.
ENGLAND. We use classical conditioning of the honeybee (Apis mellifera)
proboscis extension reflex with a visual (A) and an olfactory (X) conditioned
stimulus in a blocking paradigm. Typically, learning about one element (X) of a
compound (AX) is decreased (blocked) if the other component (A) has previously
been rewarded alone. Our results show that visual pretraining did not produce
blocking in honeybees: instead, forward pairings of A with a reward increased
subsequent learning about X relative to a backward pairing control. This finding
violates the independence assumption, which holds that elements of inter-modal
compound stimuli change associative strength independently of each other.
Furthermore, it is at odds with common theories of conditioning that predict
blocking and assume that the elements of a compound stimulus rely on one
common internal reinforcing signal. Taking the functional anatomy of the
honeybee brain into account, we suggest that vision and olfaction may not rely on
the same internal reinforcing signal; compound interactions might thus reflect the
wiring of the honeybee nervous system and the biological significance of different
sensory modalities during natural behaviour.
56. Ghee, M.; Baker, H.; Miller, J. C.; Ziff, E. B. AP-1, CREB and CBP transcription
factors differentially regulate the tyrosine hydroxylase gene. Brain-Res-Mol-
Brain-Res. 1998 Mar 30; 55(1): 101-14; ISSN: 0169-328X.
NETHERLANDS. The tyrosine hydroxylase (TH) gene encodes the rate-limiting
enzyme in the biosynthesis of catecholamines. We have investigated the roles of
two elements of the TH promoter, the TH-'Fat Specific Element' (TH-FSE) which
binds the Fos-Jun complex, and the cAMP Response Element (CRE), which
binds CREB and the co-activator protein, CREB Binding Protein (CBP) in
regulating TH gene transcription. In PC12 cells, the TH-FSE was required for
induction by NGF while the CRE was required for induction by cAMP. We show
that both elements can function independently and contribute strongly to TH
promoter basal activity in PC12 cells. We employed transient expression in the
F9 teratocarcinoma cell line to vary experimentally the levels of the nuclear
regulators implicated in TH control by the PC12 studies. In F9 cells, the TH
promoter was strongly activated by Fos and Jun, and by PKA-stimulated CREB
protein. In F9 and NIH3T3 cells, CBP, a co-activator which targets Fos-Jun and
PKA-stimulated CREB, also induced the TH promoter. Immunohistochemical
studies in rat brain regions enriched in dopaminergic neurons, including the
midbrain and olfactory bulb (OB), suggest that Fos-Jun and CREB make
differential contributions to TH gene activity in different tissues. Whereas changes
in Fos protein levels parallel decreases in TH protein upon olfactory deprivation,
CBP levels remain unchanged. This suggests that CRE-associated factors,
including CBP, are not major regulators in the OB. In contrast, the presence of
CREB and the absence of Fos immunoreactivity in midbrain dopaminergic cells
suggests that the CRE is the primary regulator in this region.. EC 1.14.16.2; EC
2.3.1.28; EC 2.7.10.-; 0; 0; 0; 0; 0; 0; 0; 0; 51-61-6; 60-92-4.
57. Gillner, S.; Mallot, H. A. Navigation and acquisition of spatial knowledge in a virtual
maze. J-Cogn-Neurosci. 1998 Jul; 10(4): 445-63; ISSN: 0898-929X.
UNITED-STATES. Spatial behavior in humans and animals includes a wide
variety of behavioral competences and makes use of a large number of sensory
cues. Here we studied the ability of human subjects to search locations, to find
shortcuts and novel paths, to estimate distances between remembered places, and
to draw sketch maps of the explored environment; these competences are related
to goal-independent memory of space, or cognitive maps. Information on spatial
relations was restricted to two types: a visual motion sequence generated by
simulated movements in a virtual maze and the subject's own movement decisions
defining the path through the maze. Visual information was local (i.e., no global
landmarks or compass information was provided). Other position and movement
information (vestibular or proprioceptive) was excluded. The amount of visual
information provided was varied over four experimental conditions. The results
indicate that human subjects are able to learn a virtual maze from sequences of
local views and movements. The information acquired is local, consisting of
recognized positions and movement decisions associated to them. Although
simple associations of this type can be shown to be present in some subjects,
more complete configurational knowledge is acquired as well. The results are
discussed in a view-based framework of navigation and the representation of
spatial knowledge by means of a view graph.
58. Gillner, S.; Mallot, H. A. Navigation and acquisition of spatial knowledge in a virtual
maze. J-Cogn-Neurosci. 1998 Jul; 10(4): 445-63; ISSN: 0898-929X.
UNITED-STATES. Spatial behavior in humans and animals includes a wide
variety of behavioral competences and makes use of a large number of sensory
cues. Here we studied the ability of human subjects to search locations, to find
shortcuts and novel paths, to estimate distances between remembered places, and
to draw sketch maps of the explored environment; these competences are related
to goal-independent memory of space, or cognitive maps. Information on spatial
relations was restricted to two types: a visual motion sequence generated by
simulated movements in a virtual maze and the subject's own movement decisions
defining the path through the maze. Visual information was local (i.e., no global
landmarks or compass information was provided). Other position and movement
information (vestibular or proprioceptive) was excluded. The amount of visual
information provided was varied over four experimental conditions. The results
indicate that human subjects are able to learn a virtual maze from sequences of
local views and movements. The information acquired is local, consisting of
recognized positions and movement decisions associated to them. Although
simple associations of this type can be shown to be present in some subjects,
more complete configurational knowledge is acquired as well. The results are
discussed in a view-based framework of navigation and the representation of
spatial knowledge by means of a view graph.
59. Gorelick, A. B.; Koshy, S. S.; Hooper, F. G.; Bennett, T. C.; Chey, W. D.; Hasler, W.
L. Differential effects of amitriptyline on perception of somatic and visceral
stimulation in healthy humans. Am-J-Physiol. 1998 Sep; 275(3 Pt 1): G460-6;
ISSN: 0002-9513.
UNITED-STATES. Tricyclic antidepressants treat chronic pain both in patients
with somatic illness and with functional bowel disorders. We compared the effects
of amitriptyline on perception of cutaneous and gastrointestinal stimulation to
assess differential analgesic effects of tricyclics on somatic and visceral pain.
Cutaneous electrical stimulation and rectal and esophageal distension were
performed before and after 21 days of double-blind 50 mg amitriptyline vs.
placebo in healthy volunteers. Amitriptyline increased currents that elicited
cutaneous threshold, moderate discomfort, and moderate pain compared with
basal (P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on
perception of rectal and esophageal distension and did not alter luminal
compliance; thus the lack of effect on perception is not due to altered visceral
elastic wall properties. In conclusion, amitriptyline reduces perception of
cutaneous stimulation but does not alter visceral perception or compliance. This
investigation demonstrates differential effects of tricyclics on somatic and visceral
afferent function in healthy humans and provides insight into mechanisms of
action in chronic pain both from somatic disease and from functional bowel
disorders.. 50-48-6.
60. Gorelick, A. B.; Koshy, S. S.; Hooper, F. G.; Bennett, T. C.; Chey, W. D.; Hasler, W.
L. Differential effects of amitriptyline on perception of somatic and visceral
stimulation in healthy humans. Am-J-Physiol. 1998 Sep; 275(3 Pt 1): G460-6;
ISSN: 0002-9513.
UNITED-STATES. Tricyclic antidepressants treat chronic pain both in patients
with somatic illness and with functional bowel disorders. We compared the effects
of amitriptyline on perception of cutaneous and gastrointestinal stimulation to
assess differential analgesic effects of tricyclics on somatic and visceral pain.
Cutaneous electrical stimulation and rectal and esophageal distension were
performed before and after 21 days of double-blind 50 mg amitriptyline vs.
placebo in healthy volunteers. Amitriptyline increased currents that elicited
cutaneous threshold, moderate discomfort, and moderate pain compared with
basal (P < 0.05), whereas placebo had no effect. Amitriptyline had no effect on
perception of rectal and esophageal distension and did not alter luminal
compliance; thus the lack of effect on perception is not due to altered visceral
elastic wall properties. In conclusion, amitriptyline reduces perception of
cutaneous stimulation but does not alter visceral perception or compliance. This
investigation demonstrates differential effects of tricyclics on somatic and visceral
afferent function in healthy humans and provides insight into mechanisms of
action in chronic pain both from somatic disease and from functional bowel
disorders.. 50-48-6.
61. Gros, B. L.; Blake, R.; Hiris, E. Anisotropies in visual motion perception: a fresh
look. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 2003-11; ISSN:
1084-7529.
UNITED-STATES. We measured motion-detection and motion-discrimination
performance for different directions of motion, using stochastic motion sequences.
Random-dot cinematograms containing 200 dots in a circular aperture were used
as stimuli in a two-interval forced-choice procedure. In the motion-detection
experiment, observers judged which of two intervals contained weak coherent
motion, the other internal containing random motion only. In the direction-
discrimination experiment, observers viewed a standard direction of motion
followed by comparison motion in a slightly different direction. Observers
indicated whether the comparison was clockwise or counterclockwise, relative to
the standard. Twelve directions of motion were tested in the detection task and
five standard directions (three cardinal directions and two oblique directions) in
the discrimination task. Detection thresholds were invariant with direction of
motion, but direction-discrimination thresholds were significantly higher for
motion in oblique directions, even at low-coherence levels. Results from control
conditions ruled out monitor artifacts and indicate that the oblique effect is
relative to retinal coordinates. These results have broad implications for
computational and physiological models of motion perception.
62. Gros, B. L.; Blake, R.; Hiris, E. Anisotropies in visual motion perception: a fresh
look. J-Opt-Soc-Am-A-Opt-Image-Sci-Vis. 1998 Aug; 15(8): 2003-11; ISSN:
1084-7529.
UNITED-STATES. We measured motion-detection and motion-discrimination
performance for different directions of motion, using stochastic motion sequences.
Random-dot cinematograms containing 200 dots in a circular aperture were used
as stimuli in a two-interval forced-choice procedure. In the motion-detection
experiment, observers judged which of two intervals contained weak coherent
motion, the other internal containing random motion only. In the direction-
discrimination experiment, observers viewed a standard direction of motion
followed by comparison motion in a slightly different direction. Observers
indicated whether the comparison was clockwise or counterclockwise, relative to
the standard. Twelve directions of motion were tested in the detection task and
five standard directions (three cardinal directions and two oblique directions) in
the discrimination task. Detection thresholds were invariant with direction of
motion, but direction-discrimination thresholds were significantly higher for
motion in oblique directions, even at low-coherence levels. Results from control
conditions ruled out monitor artifacts and indicate that the oblique effect is
relative to retinal coordinates. These results have broad implications for
computational and physiological models of motion perception.
63. Gu, M.; Owen, A. D.; Toffa, S. E.; Cooper, J. M.; Dexter, D. T.; Jenner, P.;
Marsden, C. D.; Schapira, A. H. Mitochondrial function, GSH and iron in
neurodegeneration and Lewy body diseases. J-Neurol-Sci. 1998 Jun 11; 158(1):
24-9; ISSN: 0022-510X.
NETHERLANDS. The cause of neuronal loss in patients with idiopathic
Parkinson's disease is unknown. Oxidative stress and complex I deficiency have
both been identified in the substantia nigra in Parkinson's disease but their place in
the sequence of events resulting in dopaminergic cell death is uncertain. We have
analysed respiratory chain activity, iron and reduced glutathione concentrations in
Parkinson's disease substantia innominata and in the cingulate cortex of patients
with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies to
investigate their association with neuronal death and Lewy body formation. No
abnormalities of mitochondrial function, iron or reduced glutathione levels were
identified in Parkinson's disease substantia innominata or cingulate cortex.
Mitochondrial function also appeared to be unchanged in cingulate cortex from
patients with Alzheimer's disease and from patients with dementia with Lewy
bodies, however, iron concentrations were mildly increased in both, and reduced
glutathione decreased only in Alzheimer's disease. These results confirm the
anatomic specificity of the complex I deficiency and decreased levels of reduced
glutathione within the Parkinson's disease brain and suggest that these parameters
are not associated with cholinergic cell loss in Parkinson's disease nor with Lewy
body formation in this or other diseases. We propose that our data support a
'two-hit' hypothesis for the cause of neuronal death in Parkinson's disease.. EC
1.6.99.2; 0; 51-61-6; 70-18-8; 7439-89-6.
64. Harden, D. G.; King, D.; Finlay, J. M.; Grace, A. A. Depletion of dopamine in the
prefrontal cortex decreases the basal electrophysiological activity of mesolimbic
dopamine neurons. Brain-Res. 1998 May 25; 794(1): 96-102; ISSN: 0006-8993.
NETHERLANDS. One hypothesis regarding the etiology of schizophrenia
proposes that disruption of the dopaminergic innervation of the prefrontal cortex
leads to an increase in dopamine (DA) transmission in subcortical regions. In the
present study, we examined the effect of 6-hydroxydopamine lesions of the
medial prefrontal cortex (mPFC) dopamine innervation on the spontaneous
electrophysiological activity of ventral tegmental DA neurons recorded in vivo.
DA cell activity was assessed along three dimensions: (1) the relative proportion
of DA neurons exhibiting spontaneous activity, (2) their basal firing rate, and (3)
the mean percentage of spikes fired in bursts. In lesioned rats, DA neurons in the
ventral tegmental area (VTA) exhibited a significantly slower mean firing rate, as
well as a significant reduction in the percentage of spikes fired in bursts relative to
controls. In contrast, depletion of DA in the mPFC did not have a significant
effect on the relative proportion of VTA DA neurons exhibiting spontaneous
activity. We suggest that by reducing the basal electrophysiological activity of
VTA DA neurons, mPFC DA depletion may lead to an increase in the level of
responsivity of the system to excitatory stimuli. Thus, the magnitude of increase
in action potential-dependent DA release that occurs in response to a challenge
may be augmented in lesioned rats. Copyright 1998 Elsevier Science B.V. All
rights reserved.. 1199-18-4; 51-61-6.
65. Heidbreder, C.; Feldon, J. Amphetamine-induced neurochemical and locomotor
responses are expressed differentially across the anteroposterior axis of the core
and shell subterritories of the nucleus accumbens. Synapse. 1998 Aug; 29(4): 310-
22; ISSN: 0887-4476.
UNITED-STATES. The administration of psychostimulants increases dopamine
(DA) release within the nucleus accumbens (NAC), a terminal projection site of
mesolimbic DA neurons, originating in the ventral tegmental area (VTA). Recent
evidence demonstrates that two subdivisions of the NAC, the dorsolateral core
and the ventromedial shell, can be distinguished by morphological and
immunohistochemical differences, as well as by their distinct anatomical
connections. It has been suggested that these two subregions subserve different
functions that are related to goal-directed behaviors, stimulus-reward associations,
and reinforcement induced by addictive drugs. The shell region, in particular,
modulates inputs from the limbic system, whereas the core is preferentially
innervated by nuclei that process motor information. In the present study, we
sought to investigate if (1) the direct infusion of d-amphetamine (AMPH) by
reverse microdialysis into either the core or shell of the NAC across its
anteroposterior axis differentially affects dialysate DA and 5-HT levels, and (2)
these subterritories also subserve different behavioral functions. Following the
determination of basal DA and 5-HT levels, four increasing concentrations of
AMPH (0.05, 0.10, 0.50, 1.00 microM) were substituted for the dialysis
perfusate for 60 min each. Movement units were detected by an infrared sensor
and were transmitted through a motion interface to an activity monitor analyzer.
AMPH produced a dose-dependent increase in locomotor activity after
microinfusion into either the rostral shell, caudal shell or core of the NAC. The
potency of the AMPH-induced locomotor activating effect was significantly
higher in the rostral shell of the NAC compared with the caudal shell and the core.
The lowest concentrations of AMPH (0.05, 0.1 microM) produced an equipotent
decrease in dialysate DA in either the rostral shell, caudal shell, or core. At 1.0
microM, however, AMPH selectively increased DA in the rostral shell, whereas
DA reached baseline values both in the caudal shell and core. Basal dialysate DA
levels were significantly higher in the core relative to both the rostral and caudal
parts of the shell. The highest dose of AMPH significantly increased dialysate 5-
HT levels over baseline only in the caudal shell of the NAC. The basal dialysate
5-HT levels did not significantly differ between the three subterritories of the
NAC. These results emphasize the heterogeneity and functional
compartmentalization within the NAC, the differential regulation of
neurochemical and motor responses across the anteroposterior axis of the NAC,
and the preferential effect of AMPH in the rostral shell subterritory of the NAC..
0; 300-62-9; 50-67-9; 51-61-6.
66. Heinze, H. J.; Hinrichs, H.; Scholz, M.; Burchert, W.; Mangun, G. R. Neural
mechanisms of global and local processing. A combined PET and ERP study. J-
Cogn-Neurosci. 1998 Jul; 10(4): 485-98; ISSN: 0898-929X.
UNITED-STATES. The neural mechanisms of hierarchical stimulus processing
were investigated using a combined event-related potentials (ERPs) and positron
emission tomography (PET) approach. Healthy subjects were tested under two
conditions that involved selective or divided attention between local and global
levels of hierarchical letter stimuli in order to determine whether and where
hemispheric differences might exist in the processing of local versus global
information. When attention was divided between global and local levels, the N2
component of the ERPs (260- to 360-msec latency) elicited by the target stimuli
showed asymmetries in amplitude over the two hemispheres. The N2 to local
targets was larger over the left hemisphere, but the N2 to global targets tended to
be slightly larger over the right hemisphere. However, the shorter-latency,
sensory-evoked P1 component (90- to 150-msec latency) was not different for
global versus local targets under conditions of divided attention. In contrast,
during selective attention to either global or local targets, asymmetries in the N2
component were not observed. But under selective attention conditions, the
sensory-evoked P1 components in the extrastriate cortex were enlarged for global
versus local attention. Increased regional cerebral blood flow in the posterior
fusiform gyrus bilaterally was observed in the PET data during selective attention
to either global or local targets, but neither these nor the P1 component showed
any tendency toward hemispheric difference for global versus local attention.
Neither were there any activations observed in the parietal lobe during selective
attention to global versus local targets. Together these data indicate that early
sensory inputs are not modulated to gate global versus local information
differentially into the two hemispheres. Rather, later stages of processing that
may be asymmetrically organized in the left and right hemispheres operate in
parallel to process global and local aspects of complex stimuli (i.e., the N2 effect
of the ERPs). This pattern of results supports models proposing that spatial
frequency analysis is only asymmetric at higher stages of perceptual processing
and not at the earliest stages of visual cortical analysis.
67. Heinze, H. J.; Hinrichs, H.; Scholz, M.; Burchert, W.; Mangun, G. R. Neural
mechanisms of global and local processing. A combined PET and ERP study. J-
Cogn-Neurosci. 1998 Jul; 10(4): 485-98; ISSN: 0898-929X.
UNITED-STATES. The neural mechanisms of hierarchical stimulus processing
were investigated using a combined event-related potentials (ERPs) and positron
emission tomography (PET) approach. Healthy subjects were tested under two
conditions that involved selective or divided attention between local and global
levels of hierarchical letter stimuli in order to determine whether and where
hemispheric differences might exist in the processing of local versus global
information. When attention was divided between global and local levels, the N2
component of the ERPs (260- to 360-msec latency) elicited by the target stimuli
showed asymmetries in amplitude over the two hemispheres. The N2 to local
targets was larger over the left hemisphere, but the N2 to global targets tended to
be slightly larger over the right hemisphere. However, the shorter-latency,
sensory-evoked P1 component (90- to 150-msec latency) was not different for
global versus local targets under conditions of divided attention. In contrast,
during selective attention to either global or local targets, asymmetries in the N2
component were not observed. But under selective attention conditions, the
sensory-evoked P1 components in the extrastriate cortex were enlarged for global
versus local attention. Increased regional cerebral blood flow in the posterior
fusiform gyrus bilaterally was observed in the PET data during selective attention
to either global or local targets, but neither these nor the P1 component showed
any tendency toward hemispheric difference for global versus local attention.
Neither were there any activations observed in the parietal lobe during selective
attention to global versus local targets. Together these data indicate that early
sensory inputs are not modulated to gate global versus local information
differentially into the two hemispheres. Rather, later stages of processing that
may be asymmetrically organized in the left and right hemispheres operate in
parallel to process global and local aspects of complex stimuli (i.e., the N2 effect
of the ERPs). This pattern of results supports models proposing that spatial
frequency analysis is only asymmetric at higher stages of perceptual processing
and not at the earliest stages of visual cortical analysis.
68. Hempel Jorgensen, A.; Kjaergaard, S. K.; Molhave, L. Cytological changes and
conjunctival hyperemia in relation to sensory eye irritation. Int-Arch-Occup-
Environ-Health. 1998 Jun; 71(4): 225-35; ISSN: 0340-0131.
GERMANY. In general, irritation is a physiological response to a chemical or
physical stimulus involving objective changes (e.g., local redness and edema) and
subjective sensations (e.g., pruritus and pain). The perception of an irritating
stimulus in the eyes and the upper airways is called sensory irritation. Sensory
irritation is a prevalent symptom in relation to complaints about indoor air
quality. The intensity of perceived sensory irritation in humans has mainly been
evaluated using psychophysical methods. However, perceived sensory irritation
is dependent on the subject expressing the symptoms; that is, it is a subjective
measure. This is a problem in assessment of irritation effects from air pollution or
other factors, since the expression of the irritation symptoms may be biased by,
for example, interaction with other people and odors. The subjectivity of the
measures is an important complication in several studies dealing with problems
regarding indoor air quality. The bias problems make it important to complement
the psychophysical measurements of sensory irritation with objective
assessments of irritation. In addition, only little is known about the association
between sensory irritation and possible physiological/ pathological changes in the
mucosal membranes in relation to studies of indoor air. Two studies (study 1 and
study 2) were conducted to investigate changes in conjunctival hyperemia and
conjunctival fluid cytology for subjects exposed to volatile organic compounds
(VOCs) in their eyes only. Eight subjects participated in study 1. Each subject
was exposed to three different mixtures of VOCs. A total of 16 subjects
participated in study 2. Half of the subjects were exposed to 1-octene and the
other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were
taken and conjunctival fluid was sampled before and after exposure. Moreover,
the perceived irritation intensities were registered continuously during exposure.
Overall, perceived irritation intensity and conjunctival hyperemia increased with
increasing exposure concentrations, whereas cytological changes in the
conjunctival fluid samples did not seen to be related to exposure concentration,
perceived irritation, or changes in conjunctival hyperemia.. 0; 0.
69. Hempel Jorgensen, A.; Kjaergaard, S. K.; Molhave, L. Cytological changes and
conjunctival hyperemia in relation to sensory eye irritation. Int-Arch-Occup-
Environ-Health. 1998 Jun; 71(4): 225-35; ISSN: 0340-0131.
GERMANY. In general, irritation is a physiological response to a chemical or
physical stimulus involving objective changes (e.g., local redness and edema) and
subjective sensations (e.g., pruritus and pain). The perception of an irritating
stimulus in the eyes and the upper airways is called sensory irritation. Sensory
irritation is a prevalent symptom in relation to complaints about indoor air
quality. The intensity of perceived sensory irritation in humans has mainly been
evaluated using psychophysical methods. However, perceived sensory irritation
is dependent on the subject expressing the symptoms; that is, it is a subjective
measure. This is a problem in assessment of irritation effects from air pollution or
other factors, since the expression of the irritation symptoms may be biased by,
for example, interaction with other people and odors. The subjectivity of the
measures is an important complication in several studies dealing with problems
regarding indoor air quality. The bias problems make it important to complement
the psychophysical measurements of sensory irritation with objective
assessments of irritation. In addition, only little is known about the association
between sensory irritation and possible physiological/ pathological changes in the
mucosal membranes in relation to studies of indoor air. Two studies (study 1 and
study 2) were conducted to investigate changes in conjunctival hyperemia and
conjunctival fluid cytology for subjects exposed to volatile organic compounds
(VOCs) in their eyes only. Eight subjects participated in study 1. Each subject
was exposed to three different mixtures of VOCs. A total of 16 subjects
participated in study 2. Half of the subjects were exposed to 1-octene and the
other half, to n-butanol. In both studies, photographs of bulbar conjunctiva were
taken and conjunctival fluid was sampled before and after exposure. Moreover,
the perceived irritation intensities were registered continuously during exposure.
Overall, perceived irritation intensity and conjunctival hyperemia increased with
increasing exposure concentrations, whereas cytological changes in the
conjunctival fluid samples did not seen to be related to exposure concentration,
perceived irritation, or changes in conjunctival hyperemia.. 0; 0.
70. Hershey, T.; Black, K. J.; Stambuk, M. K.; Carl, J. L.; McGee Minnich, L. A.;
Perlmutter, J. S. Altered thalamic response to levodopa in Parkinson's patients
with dopa-induced dyskinesias. Proc-Natl-Acad-Sci-U-S-A. 1998 Sep 29; 95(20):
12016-21; ISSN: 0027-8424.
UNITED-STATES. Parkinson's disease (PD) is a progressive neurologic
condition characterized by tremor, slowness, stiffness, and unstable posture.
Degeneration of dopamine-producing neurons in the substantia nigra causes PD.
Treatment with levodopa, a precursor of dopamine, initially ameliorates the
clinical manifestations of PD. However, chronic levodopa treatment can produce
severe involuntary movements (so-called dopa-induced dyskinesias or DID),
limiting treatment. Pallidotomy, placement of a surgical lesion in the internal
segment of the globus pallidus, reduces DID. Because this result is inconsistent
with current theories of both basal ganglia function and DID, it prompted us to
investigate the brain's response to levodopa. We measured regional cerebral blood
flow response to levodopa with positron-emission tomography in 6 PD patients
with DID, 10 chronically treated PD patients without DID, 17 dopa-naive PD
patients, and 11 normals. The dose of levodopa was chosen to produce clinical
benefit without inducing DID. This strategy allowed us to examine the brain
response to levodopa across groups without the confounding effect of differences
in motor behavior. We found that the DID group had a significantly greater
response in ventrolateral thalamus than the other groups. This was associated
with decreased activity in primary motor cortex. These findings are consistent
with increased inhibitory output from the internal segment of the globus pallidus
to thalamus after levodopa administration. They provide a physiological
explanation for the clinical efficacy of pallidotomy and new insights into the
physiology of the basal ganglia.. 0; 38821-49-7.
71. Herz, A. Opioid reward mechanisms: a key role in drug abuse? Can-J-Physiol-
Pharmacol. 1998 Mar; 76(3): 252-8; ISSN: 0008-4212.
CANADA. There is increasing evidence to implicate the mesolimbic dopamine
system in the rewarding effects of drugs of abuse such as opioids,
psychostimulants, and alcohol, and in addition endogenous opioids may play a
key role in the underlying adaptive mechanisms. Opioid agonists with affinity for
mu and delta opioid receptors are rewarding, whereas opioid agonists with affinity
for kappa receptors are aversive. These opposing motivational effects are
paralleled by an increase and decrease, respectively, of dopamine release in the
nucleus accumbens. Opposite effects are induced in response to selective
antagonists for these different receptor types, pointing to tonically active
endogenous opioid reward mechanisms. Withdrawal from chronic morphine
results in sensitization for opioid reward; an effect that is counteracted by kappa
opioid agonists. The rewarding effects of psychostimulants such as cocaine and
amphetamine, mediated by the mesolimbic dopamine pathway, are modulated by
opioid mechanisms in both directions: sensitization by morphine pretreatment,
inhibition by kappa receptor agonists. A modulatory role of endogenous opioids
is also suggested from biochemical data, showing increased dynorphin and kappa
receptor expression after chronic cocaine treatment. Alcohol reward involves the
mesolimbic reward system also, and opioids modulate this behaviour. Naltrexone
as well as selective mu and delta opioid receptor antagonists decrease alcohol
consumption in operant conditioning models. Biochemical approaches point to a
functional deficit of endogenous opioids in genetic models exhibiting high
prevalence for alcohol intake. The therapeutic implications of these data are
discussed.. 0; 0; 0.
72. Hillyard, S. A.; Teder Salejarvi, W. A.; Munte, T. F. Temporal dynamics of early
perceptual processing. Curr-Opin-Neurobiol. 1998 Apr; 8(2): 202-10; ISSN:
0959-4388.
ENGLAND. Recordings of electrical and magnetic brain responses to sensory
stimulation provide high-resolution measures of the time course of early
perceptual processing. Spatio-temporal analyses of brain activity patterns during
the first 200 ms after stimulus presentation have characterized the timing of
attentional selection processes and different stages of feature encoding and pattern
analyses. Recent studies that incorporate blood flow neuroimaging techniques
provide support for mechanisms of early selection of attended visual inputs in
extrastriate cortical pathways. The spatial tuning properties of early auditory
selection have also been delineated. Electrical and magnetic responses that index
the encoding of higher-order pattern information have been identified in both
visual and auditory modalities and localized to specific cortical areas.
73. Hillyard, S. A.; Teder Salejarvi, W. A.; Munte, T. F. Temporal dynamics of early
perceptual processing. Curr-Opin-Neurobiol. 1998 Apr; 8(2): 202-10; ISSN:
0959-4388.
ENGLAND. Recordings of electrical and magnetic brain responses to sensory
stimulation provide high-resolution measures of the time course of early
perceptual processing. Spatio-temporal analyses of brain activity patterns during
the first 200 ms after stimulus presentation have characterized the timing of
attentional selection processes and different stages of feature encoding and pattern
analyses. Recent studies that incorporate blood flow neuroimaging techniques
provide support for mechanisms of early selection of attended visual inputs in
extrastriate cortical pathways. The spatial tuning properties of early auditory
selection have also been delineated. Electrical and magnetic responses that index
the encoding of higher-order pattern information have been identified in both
visual and auditory modalities and localized to specific cortical areas.
74. Hilz, M. J.; Kolodny, E. H.; Neuner, I.; Stemper, B.; Axelrod, F. B. Highly abnormal
thermotests in familial dysautonomia suggest increased cardiac autonomic risk. J-
Neurol-Neurosurg-Psychiatry. 1998 Sep; 65(3): 338-43; ISSN: 0022-3050.
ENGLAND. OBJECTIVE: Patients with familial dysautonomia have an
increased risk of sudden death. In some patients with familial dysautonomia,
sympathetic cardiac dysfunction is indicated by prolongation of corrected QT
(QTc) interval, especially during stress tests. As many patients do not tolerate
physical stress, additional indices are needed to predict autonomic risk. In familial
dysautonomia there is a reduction of both sympathetic neurons and peripheral
small nerve fibres which mediate temperature perception. Consequently,
quantitative thermal perception test results might correlate with QTc values. If
this assumption is correct, quantitative thermotesting could contribute to
predicting increased autonomic risk. METHODS: To test this hypothesis, QTc
intervals were determined in 12 male and eight female patients with familial
dysautonomia, aged 10 to 41 years (mean 21.7 (SD 10.1) years), in supine and
erect positions and postexercise and correlated with warm and cold perception
thresholds assessed at six body sites using a Thermotest. RESULTS: Due to
orthostatic presyncope, six patients were unable to undergo erect and postexercise
QTc interval assessment. The QTc interval was prolonged (>440 ms) in two
patients when supine and in two additional patients when erect and postexercise.
Supine QTc intervals correlated significantly with thermal threshold values at the
six body sites and with the number of sites with abnormal thermal perception
(Spearman's rank correlation p<0.05). Abnormal Thermotest results were more
frequent in the four patients with QTc prolongation and the six patients with
intolerance to stress tests. CONCLUSION: The results suggest that impaired
thermal perception correlates with cardiac sympathetic dysfunction in patients
with familial dysautonomia. Thus thermotesting may provide an alternative, albeit
indirect, means of assessing sympathetic dysfunction in autonomic disorders.
75. Hilz, M. J.; Kolodny, E. H.; Neuner, I.; Stemper, B.; Axelrod, F. B. Highly abnormal
thermotests in familial dysautonomia suggest increased cardiac autonomic risk. J-
Neurol-Neurosurg-Psychiatry. 1998 Sep; 65(3): 338-43; ISSN: 0022-3050.
ENGLAND. OBJECTIVE: Patients with familial dysautonomia have an
increased risk of sudden death. In some patients with familial dysautonomia,
sympathetic cardiac dysfunction is indicated by prolongation of corrected QT
(QTc) interval, especially during stress tests. As many patients do not tolerate
physical stress, additional indices are needed to predict autonomic risk. In familial
dysautonomia there is a reduction of both sympathetic neurons and peripheral
small nerve fibres which mediate temperature perception. Consequently,
quantitative thermal perception test results might correlate with QTc values. If
this assumption is correct, quantitative thermotesting could contribute to
predicting increased autonomic risk. METHODS: To test this hypothesis, QTc
intervals were determined in 12 male and eight female patients with familial
dysautonomia, aged 10 to 41 years (mean 21.7 (SD 10.1) years), in supine and
erect positions and postexercise and correlated with warm and cold perception
thresholds assessed at six body sites using a Thermotest. RESULTS: Due to
orthostatic presyncope, six patients were unable to undergo erect and postexercise
QTc interval assessment. The QTc interval was prolonged (>440 ms) in two
patients when supine and in two additional patients when erect and postexercise.
Supine QTc intervals correlated significantly with thermal threshold values at the
six body sites and with the number of sites with abnormal thermal perception
(Spearman's rank correlation p<0.05). Abnormal Thermotest results were more
frequent in the four patients with QTc prolongation and the six patients with
intolerance to stress tests. CONCLUSION: The results suggest that impaired
thermal perception correlates with cardiac sympathetic dysfunction in patients
with familial dysautonomia. Thus thermotesting may provide an alternative, albeit
indirect, means of assessing sympathetic dysfunction in autonomic disorders.
76. Hirsch, E. C.; Hunot, S.; Damier, P.; Faucheux, B. Glial cells and inflammation in
Parkinson's disease: a role in neurodegeneration? Ann-Neurol. 1998 Sep; 44(3
Suppl 1): S115-20; ISSN: 0364-5134.
UNITED-STATES. The data reviewed here show that, in Parkinson's disease
(PD), some dopaminergic neurons are more vulnerable than others to the
pathologic process. The glial cells surrounding dopaminergic neurons may be
involved in this selective vulnerability. One subpopulation of glial cells, in
particular, may play a neuroprotective role by metabolizing dopamine and
scavenging oxygen free radicals that are associated with dopamine metabolism.
Another subpopulation of glial cells may be deleterious to dopaminergic neurons.
This effect may be mediated by the production of nitric oxide and cytokines,
which may in turn account for the oxidative stress observed in the substantia nigra
of patients with PD. Finally, this inflammatory reaction may result in the
induction of apoptosis.. 0; 51-61-6.
77. Hoffmann, K. P.; Distler, C.; Grusser, O. J. Optokinetic reflex in squirrel monkeys
after long-term monocular deprivation. Eur-J-Neurosci. 1998 Mar; 10(3): 1136-
44; ISSN: 0953-816X.
FRANCE. Horizontal optokinetic nystagmus (OKN) as well as neuronal
response properties in the nucleus of the optic tract and the dorsal terminal
nucleus of the accessory optic system (NOT-DTN) were investigated in three
monocularly deprived squirrel monkeys. In two monkeys occlusion of one eye
was performed at birth (early) and in the third after 7 weeks (late). In adulthood,
in early deprived monkeys monocular horizontal OKN tested through the non-
deprived eye was symmetrical and in no way different from normal, i.e.
stimulation in the temporonasal and nasotemporal direction elicited equal and
robust responses. OKN through the early occluded eye, however, was grossly
abnormal with low gain and great variability in the consistency of nasotemporal
and temporonasal slow phase eye movements. When in the late deprived monkey
the non-deprived eye was occluded a strong spontaneous nystagmus developed
despite the deprived eye viewing a stationary pattern. The slow phases were
directed from nasal to temporal for the deprived eye. When tested through the
non-deprived eye all neuronal responses of the NOT-DTN were normal. The
deprived eye's influence on NOT-DTN neurons was extremely weak. No neuron
with a moderate or even dominant input from the deprived eye was found after
early deprivation. In the late deprived case the deficit was not as severe but still
the non-deprived eye was clearly dominating the responses in all neurons tested.
Velocity tuning of neurons tested through the non-deprived eye was normal and
qualitatively corresponded well to slow phase eye velocity in response to
equivalent retinal slip during OKN. Through the early deprived eye, however,
velocity tuning was extremely poor. It was somewhat better through the late
deprived eye. We suggest that the dramatic deterioration in the optokinetic reflex
found after long-term monocular deprivation for the amblyopic eye is probably
caused by the almost complete loss of retinal and cortical input driven by that eye
to the NOT-DTN. These results are discussed in relation to our previous results
in cats and reports in the literature for humans with occlusion amblyopia.
78. Hoffmann, K. P.; Distler, C.; Grusser, O. J. Optokinetic reflex in squirrel monkeys
after long-term monocular deprivation. Eur-J-Neurosci. 1998 Mar; 10(3): 1136-
44; ISSN: 0953-816X.
FRANCE. Horizontal optokinetic nystagmus (OKN) as well as neuronal
response properties in the nucleus of the optic tract and the dorsal terminal
nucleus of the accessory optic system (NOT-DTN) were investigated in three
monocularly deprived squirrel monkeys. In two monkeys occlusion of one eye
was performed at birth (early) and in the third after 7 weeks (late). In adulthood,
in early deprived monkeys monocular horizontal OKN tested through the non-
deprived eye was symmetrical and in no way different from normal, i.e.
stimulation in the temporonasal and nasotemporal direction elicited equal and
robust responses. OKN through the early occluded eye, however, was grossly
abnormal with low gain and great variability in the consistency of nasotemporal
and temporonasal slow phase eye movements. When in the late deprived monkey
the non-deprived eye was occluded a strong spontaneous nystagmus developed
despite the deprived eye viewing a stationary pattern. The slow phases were
directed from nasal to temporal for the deprived eye. When tested through the
non-deprived eye all neuronal responses of the NOT-DTN were normal. The
deprived eye's influence on NOT-DTN neurons was extremely weak. No neuron
with a moderate or even dominant input from the deprived eye was found after
early deprivation. In the late deprived case the deficit was not as severe but still
the non-deprived eye was clearly dominating the responses in all neurons tested.
Velocity tuning of neurons tested through the non-deprived eye was normal and
qualitatively corresponded well to slow phase eye velocity in response to
equivalent retinal slip during OKN. Through the early deprived eye, however,
velocity tuning was extremely poor. It was somewhat better through the late
deprived eye. We suggest that the dramatic deterioration in the optokinetic reflex
found after long-term monocular deprivation for the amblyopic eye is probably
caused by the almost complete loss of retinal and cortical input driven by that eye
to the NOT-DTN. These results are discussed in relation to our previous results
in cats and reports in the literature for humans with occlusion amblyopia.
79. Honey, C. R.; Shen, H. Circling behaviour in 6-hydroxydopamine-lesioned rats given
pulsed levodopa is reduced more by lesions in the entopeduncular
nucleus/substantia nigra pars reticulata than in the subthalamic nucleus. Neurosci-
Lett. 1998 Jun 19; 249(2-3): 151-4; ISSN: 0304-3940.
IRELAND. Rats unilaterally lesioned with 6-hydroxydopamine to deplete
striatal dopamine received daily injections of levodopa methyl ester in
combination with benserazide. Delayed lesions in the subthalamic nucleus (Group
2) or entopeduncular nucleus and substantia nigra par reticulata (Group 3) were
made, unilateral to the dopamine depletion. Apomorphine-induced rotation was
significantly reduced in Group 2 versus sham-operated controls (P < 0.006) and in
Group 3 versus Group 2 (P < 0.03). Results suggest that enhanced apomorphine-
induced rotation in this model is mediated through both the striatopallidal and
striatonigral pathway.. 0; 0; 0; 0; 1199-18-4; 322-35-0; 58-00-4; 89-00-9.
80. Huang, K. X.; Bergstrom, D. A.; Ruskin, D. N.; Walters, J. R. N-methyl-D-aspartate
receptor blockade attenuates D1 dopamine receptor modulation of neuronal
activity in rat substantia nigra. Synapse. 1998 Sep; 30(1): 18-29; ISSN: 0887-
4476.
UNITED-STATES. It has been proposed that dopamine and glutamate affect
basal ganglia output, in part, through interactions between D1 receptors and
NMDA receptors. The present study examined whether N-methyl-D-aspartate
(NMDA) receptor antagonists affect the neurophysiological responses of
substantia nigra pars compacta (SNpc; dopaminergic) and pars reticulata (SNpr;
non-dopaminergic) neurons to a systemically administered D1 dopamine agonist
in two animals models of Parkinson's disease, reserpine treatment and nigrostriatal
lesion. Previous studies using extracellular single unit recording techniques have
shown that the D1 dopamine agonist SKF 38393 (10 mg/kg) exerts different
effects on the firing rates of SNpr neurons after these two dopamine-depleting
treatments, suggesting the involvement of multiple mechanisms. SKF 38393
consistently increased the firing rates of SNpr neurons in rats treated
subchronically with reserpine, and markedly decreased SNpr firing rates in rats
with nigrostriatal damage. Pretreatment with the non-competitive NMDA
antagonist MK-801 (0.15 mg/kg i.v.) blocked, and the competitive NMDA
antagonist (+/-)-CPP (30 mg/kg i.p.) attenuated, the rate effects of SKF 38393 in
both dopamine-depleted preparations. SKF 38393 consistently inhibited the firing
rate of SNpc dopamine neurons after acute reserpine treatment (10 mg/kg, 4-7
hours), an effect specifically mediated by D1 receptors. Pretreatment with MK-
801 (0.1 mg/kg i.v.) or the competitive NMDA antagonist (+)-HA-966 (30 mg/kg
i.v.) also effectively attenuated SKF 38393's inhibitory effect on SNpc dopamine
neurons. Therefore, NMDA receptor blockade markedly reduces the ability of D1
receptor stimulation to modulate firing rates of both dopaminergic and non-
dopaminergic cells in the substantia nigra. Although multiple mechanisms appear
to underlie D1-mediated effects on substantia nigra firing rates in reserpine and 6-
OHDA-treated rats, these results demonstrate a common dependence on
glutamatergic transmission and a permissive role for NMDA receptor activation in
the ability of D1 receptor stimulation to both enhance and reduce neuronal
activity in the substantia nigra.. 0; 0; 0; 0; 0; 100828-16-8; 1199-18-4; 50-55-5;
67287-49-4; 77086-22-7; 87075-17-0.
81. Huckins, S. C.; Turner, C. W.; Doherty, K. A.; Fonte, M. M.; Szeverenyi, N. M.
Functional magnetic resonance imaging measures of blood flow patterns in the
human auditory cortex in response to sound. J-Speech-Lang-Hear-Res. 1998 Jun;
41(3): 538-48; ISSN: 1092-4388.
UNITED-STATES. Functional Magnetic Resonance Imaging (fMRI) holds
exciting potential as a research and clinical tool for exploring the human auditory
system. This noninvasive technique allows the measurement of discrete changes in
cerebral cortical blood flow in response to sensory stimuli, allowing determination
of precise neuroanatomical locations of the underlying brain parenchymal activity.
Application of fMRI in auditory research, however, has been limited. One
problem is that fMRI utilizing echo-planar imaging technology (EPI) generates
intense noise that could potentially affect the results of auditory experiments.
Also, issues relating to the reliability of fMRI for listeners with normal hearing
need to be resolved before this technique can be used to study listeners with
hearing loss. This preliminary study examines the feasibility of using fMRI in
auditory research by performing a simple set of experiments to test the reliability
of scanning parameters that use a high resolution and high signal-to-noise ratio
unlike that presently reported in the literature. We used consonant-vowel (CV)
speech stimuli to investigate whether or not we could observe reproducible and
consistent changes in cortical blood flow in listeners during a single scanning
session, across more than one scanning session, and in more than one listener. In
addition, we wanted to determine if there were differences between CV speech
and nonspeech complex stimuli across listeners. Our study shows reproducibility
within and across listeners for CV speech stimuli. Results were reproducible for
CV speech stimuli within fMRI scanning sessions for 5 out of 9 listeners and
were reproducible for 6 out of 8 listeners across fMRI scanning sessions. Results
of nonspeech complex stimuli across listeners showed activity in 4 out of 9
individuals tested.
82. Huckins, S. C.; Turner, C. W.; Doherty, K. A.; Fonte, M. M.; Szeverenyi, N. M.
Functional magnetic resonance imaging measures of blood flow patterns in the
human auditory cortex in response to sound. J-Speech-Lang-Hear-Res. 1998 Jun;
41(3): 538-48; ISSN: 1092-4388.
UNITED-STATES. Functional Magnetic Resonance Imaging (fMRI) holds
exciting potential as a research and clinical tool for exploring the human auditory
system. This noninvasive technique allows the measurement of discrete changes in
cerebral cortical blood flow in response to sensory stimuli, allowing determination
of precise neuroanatomical locations of the underlying brain parenchymal activity.
Application of fMRI in auditory research, however, has been limited. One
problem is that fMRI utilizing echo-planar imaging technology (EPI) generates
intense noise that could potentially affect the results of auditory experiments.
Also, issues relating to the reliability of fMRI for listeners with normal hearing
need to be resolved before this technique can be used to study listeners with
hearing loss. This preliminary study examines the feasibility of using fMRI in
auditory research by performing a simple set of experiments to test the reliability
of scanning parameters that use a high resolution and high signal-to-noise ratio
unlike that presently reported in the literature. We used consonant-vowel (CV)
speech stimuli to investigate whether or not we could observe reproducible and
consistent changes in cortical blood flow in listeners during a single scanning
session, across more than one scanning session, and in more than one listener. In
addition, we wanted to determine if there were differences between CV speech
and nonspeech complex stimuli across listeners. Our study shows reproducibility
within and across listeners for CV speech stimuli. Results were reproducible for
CV speech stimuli within fMRI scanning sessions for 5 out of 9 listeners and
were reproducible for 6 out of 8 listeners across fMRI scanning sessions. Results
of nonspeech complex stimuli across listeners showed activity in 4 out of 9
individuals tested.
83. Ichikawa, J.; Kuroki, T.; Meltzer, H. Y. Differential effects of chronic imipramine and
fluoxetine on basal and amphetamine-induced extracellular dopamine levels in rat
nucleus accumbens. Eur-J-Pharmacol. 1998 Jun 5; 350(2-3): 159-64; ISSN: 0014-
2999.
NETHERLANDS. The effect of chronic treatment with the tricyclic
antidepressant drug, imipramine (10 mg/kg per day), the selective serotonin (5-
HT) reuptake inhibitor, fluoxetine hydrochloride (10 mg/kg per day), and vehicle,
in drinking water for 24-28 days followed by 3-5 days withdrawal, on
extracellular dopamine levels was studied in rat nucleus accumbens by in vivo
microdialysis. Basal extracellular dopamine levels in the nucleus accumbens were
increased after chronic imipramine (12.7 +/- 1.5 fmol/20 microl per 30 min, P =
0.019), and moderately decreased after chronic fluoxetine (6.5 +/- 0.6, P = 0.047),
as compared to the vehicle controls (9.1 +/- 0.7), determined by one-way analysis
of variance (ANOVA). Repeated measure ANOVA indicated that the D-
amphetamine sulfate (0.5 mg/kg, s.c.)-induced increase in extracellular dopamine
levels in the nucleus accumbens was potentiated after chronic imipramine (P =
0.002), but unchanged after chronic fluoxetine (P = 0.83). The difference in the
effect of amphetamine could be influenced by the significant differences in basal
levels. However, these results were also confirmed by analysis of the net area
under the curve (net-AUC) for a 180-min period (six samples): for chronic
imipramine (337 +/- 45 fmol/180 min, P = 0.005) and chronic fluoxetine (249 +/-
38, P = 0.57), as compared to the vehicle controls (178 +/- 29), determined by
one-way ANOVA. We suggest that the effect of treatment with these agents on
mesolimbic dopamine is unlikely to be involved in their shared antidepressant
action, but may be relevant to other aspects of the therapeutic profile of these
two drugs, e.g. the switch into mania which is more common after treatment with
imipramine than fluoxetine and exacerbation of positive symptoms in patients
with schizophrenia or schizoaffective disorder.. 0; 0; 0; 300-62-9; 50-49-7; 51-
61-6; 54910-89-3.
84. Ison, J. R.; Agrawal, P.; Pak, J.; Vaughn, W. J. Changes in temporal acuity with age
and with hearing impairment in the mouse: a study of the acoustic startle reflex
and its inhibition by brief decrements in noise level. J-Acoust-Soc-Am. 1998 Sep;
104(3 Pt 1): 1696-704; ISSN: 0001-4966.
UNITED-STATES. Temporal acuity for brief gaps in noise was studied in mice
of different ages (1-36 months) from strains with differing susceptibility to age-
related hearing loss, using reflex modification audiometry. Prepulse inhibition of
the acoustic startle reflex (ASR) increased with gap depth (GD: 10-40 dB in 70
dB SPL noise) and lead time (LT: 1-15 ms). The increase in inhibition with LT
followed an exponential function in which the two parameters, asymptotic
inhibition (AINH) and the time constant (tau), were both affected by GD. AINH
rapidly declined from 1 to 6 and then to 18 months of age in C57BL/6J mice with
progressively severe hearing loss, but first increased with maturation and then
gradually declined beyond 6-12 months of age in CBA/CaJ and CBA x C57BL Fl-
hybrid mice, which show no apparent change in sensory function at these ages. In
contrast, tau was unaffected by hearing loss or by age, this suggesting that age-
related changes in this form of temporal acuity occur because of a reduction in the
efficiency with which gaps are centrally processed, not from any reduced ability
to follow their rapid shift in noise level.
85. Ison, J. R.; Agrawal, P.; Pak, J.; Vaughn, W. J. Changes in temporal acuity with age
and with hearing impairment in the mouse: a study of the acoustic startle reflex
and its inhibition by brief decrements in noise level. J-Acoust-Soc-Am. 1998 Sep;
104(3 Pt 1): 1696-704; ISSN: 0001-4966.
UNITED-STATES. Temporal acuity for brief gaps in noise was studied in mice
of different ages (1-36 months) from strains with differing susceptibility to age-
related hearing loss, using reflex modification audiometry. Prepulse inhibition of
the acoustic startle reflex (ASR) increased with gap depth (GD: 10-40 dB in 70
dB SPL noise) and lead time (LT: 1-15 ms). The increase in inhibition with LT
followed an exponential function in which the two parameters, asymptotic
inhibition (AINH) and the time constant (tau), were both affected by GD. AINH
rapidly declined from 1 to 6 and then to 18 months of age in C57BL/6J mice with
progressively severe hearing loss, but first increased with maturation and then
gradually declined beyond 6-12 months of age in CBA/CaJ and CBA x C57BL Fl-
hybrid mice, which show no apparent change in sensory function at these ages. In
contrast, tau was unaffected by hearing loss or by age, this suggesting that age-
related changes in this form of temporal acuity occur because of a reduction in the
efficiency with which gaps are centrally processed, not from any reduced ability
to follow their rapid shift in noise level.
86. Jentsch, J. D.; Tran, A.; Taylor, J. R.; Roth, R. H. Prefrontal cortical involvement in
phencyclidine-induced activation of the mesolimbic dopamine system: behavioral
and neurochemical evidence. Psychopharmacology-Berl. 1998 Jul; 138(1): 89-95;
ISSN: 0033-3158.
GERMANY. Acute administration of phencyclidine to rats potently activates
mesocorticolimbic dopaminergic neurons. The activation of dopamine release and
utilization in the prefrontal cortex and nucleus accumbens are associated with
profound cognitive impairment and hyperlocomotion, respectively. This
dopaminergic activation by phencyclidine is not mediated by direct effects on the
cell body regions of the dopamine neurons; however, phencyclidine augments
dopamine release locally in the terminal fields. In the present study, the possible
involvement of the prefrontal cortex in mediating activation of the mesolimbic
dopamine system by phencyclidine was examined. Ibotenic acid lesions of the
prefrontal cortex attenuated the biochemical activation of the mesolimbic
dopamine neurons by PCP, and prefrontal lesions sharply blunted phencyclidine-,
but not amphetamine- or novelty-, induced hyperlocomotion. In addition,
injection of phencyclidine directly into the prefrontal cortex increased dopamine
utilization in the nucleus accumbens and induced hyperlocomotion. In summary,
these studies show that phencyclidine activates the mesolimbic pathway through
a mechanism in the prefrontal cortex, possibly by disinhibiting the cortical circuit
and activating corticofugal glutamatergic release in the ventral tegmental area.. 0;
0; 0; 51-61-6; 77-10-1.
87. Johansson, G.; Ahlstrom, U. Visual bridging of empty gaps in the optic flow.
Percept-Psychophys. 1998 Aug; 60(6): 915-25; ISSN: 0031-5117.
UNITED-STATES. This is a study of perception of bending motion and jointed
rigid motions over large invisible segments of a bending line. In this project, we
investigated the visual perception of changing form of lines, built up by a series of
dots and presented under highly reduced pictorial conditions. The changing form
was indicated by one or two moving and continuously changing visible fragments
of the line. The most extreme condition studied was the perception of the bending
of an initially vertical 24-dot line, visually represented only by the stationary base
dot and the two moving dots at its top. In this experiment, nearly all subjects
reported experiencing a smooth bending connection over the 21-dot empty gap.
Three experiments are described and analyzed. The results suggest that the human
visual system is astonishingly well adapted for derivation of relevant figural
information from such severely reduced, continuously changing optical
presentation. An explanation in terms of automatic sensory mechanisms related to
the physiological receptive field effect is proposed.
88. Johansson, G.; Ahlstrom, U. Visual bridging of empty gaps in the optic flow.
Percept-Psychophys. 1998 Aug; 60(6): 915-25; ISSN: 0031-5117.
UNITED-STATES. This is a study of perception of bending motion and jointed
rigid motions over large invisible segments of a bending line. In this project, we
investigated the visual perception of changing form of lines, built up by a series of
dots and presented under highly reduced pictorial conditions. The changing form
was indicated by one or two moving and continuously changing visible fragments
of the line. The most extreme condition studied was the perception of the bending
of an initially vertical 24-dot line, visually represented only by the stationary base
dot and the two moving dots at its top. In this experiment, nearly all subjects
reported experiencing a smooth bending connection over the 21-dot empty gap.
Three experiments are described and analyzed. The results suggest that the human
visual system is astonishingly well adapted for derivation of relevant figural
information from such severely reduced, continuously changing optical
presentation. An explanation in terms of automatic sensory mechanisms related to
the physiological receptive field effect is proposed.
89. Johnson, M. H.; Breakwell, G.; Douglas, W.; Humphries, S. The effects of imagery
and sensory detection distractors on different measures of pain: how does
distraction work? Br-J-Clin-Psychol. 1998 May; 37( Pt 2): 141-54; ISSN: 0144-
6657.
ENGLAND. OBJECTIVES: Two experiments compared the effects of different
distraction tasks on pain. Based on multiple-resource theory, Expt 1 predicted
that the more a distractor shares processing resources with pain perception the
greater the interference between the two. Experiment 2 tested whether the
emotional content of the distractor would differentially effect measures that are
supposedly reflective of the affective component of pain. DESIGN: Both
experiments used repeated measures designs, with counterbalanced distraction
conditions. METHODS: In Expt 1 20 participants indicated their pain threshold.
No instructions, or one of three distraction conditions were presented across four
blocks of potassium iontophoresis. The distractors were: thermal and light
detection, and neutral imagining. In Expt 2 30 participants had three blocks of
pain threshold, pain tolerance, and pain rating trials. For threshold, tolerance, and
rating trials, one block was without distraction, a second block was completed
during light detection, and a third block while imagining an enjoyable holiday.
RESULTS: In Expt 1 all the distractors increased pain threshold. The two
detection tasks were similarly effective, and more so than the imagination task.
Performance on the two detection tasks was impaired by painful stimulation
similarly for both tasks. In Expt 2 the visual detection distractor increased pain
threshold and tolerance and reduced pain ratings while pleasant imagery only
increased pain threshold. CONCLUSIONS: These results indicate that a task that
requires attention to external cues has more impact on pain than either a positive
or neutral imagination task. However, it is not clear that the specific resources
used by the distraction tasks moderated pain differentially as predicted by
multiple-resource theory.
90. Johnson, M. H.; Breakwell, G.; Douglas, W.; Humphries, S. The effects of imagery
and sensory detection distractors on different measures of pain: how does
distraction work? Br-J-Clin-Psychol. 1998 May; 37( Pt 2): 141-54; ISSN: 0144-
6657.
ENGLAND. OBJECTIVES: Two experiments compared the effects of different
distraction tasks on pain. Based on multiple-resource theory, Expt 1 predicted
that the more a distractor shares processing resources with pain perception the
greater the interference between the two. Experiment 2 tested whether the
emotional content of the distractor would differentially effect measures that are
supposedly reflective of the affective component of pain. DESIGN: Both
experiments used repeated measures designs, with counterbalanced distraction
conditions. METHODS: In Expt 1 20 participants indicated their pain threshold.
No instructions, or one of three distraction conditions were presented across four
blocks of potassium iontophoresis. The distractors were: thermal and light
detection, and neutral imagining. In Expt 2 30 participants had three blocks of
pain threshold, pain tolerance, and pain rating trials. For threshold, tolerance, and
rating trials, one block was without distraction, a second block was completed
during light detection, and a third block while imagining an enjoyable holiday.
RESULTS: In Expt 1 all the distractors increased pain threshold. The two
detection tasks were similarly effective, and more so than the imagination task.
Performance on the two detection tasks was impaired by painful stimulation
similarly for both tasks. In Expt 2 the visual detection distractor increased pain
threshold and tolerance and reduced pain ratings while pleasant imagery only
increased pain threshold. CONCLUSIONS: These results indicate that a task that
requires attention to external cues has more impact on pain than either a positive
or neutral imagination task. However, it is not clear that the specific resources
used by the distraction tasks moderated pain differentially as predicted by
multiple-resource theory.
91. Kawashima, T.; Iwaki, T.; Yamamoto, K.; Doi, K.; Kudo, T. [Predictive factors for
speech perception in patients with cochlear implant]. Nippon-Jibiinkoka-Gakkai-
Kaiho. 1998 Jun; 101(6): 829-35; ISSN: 0030-6622.
JAPAN. Cochlear implant therapy is an epoch-making advance in artificial
sensory organ transplants, but the positive effects on speech perception vary.
Quantification theory type I, a multivariate analysis, was used to determine
predictive factors for speech perception in patients with cochlear implants. Fifty-
one postlingual deaf adults (18 male and 33 female, mean age, 53.4, mean duration
of deafness, 8.6 years) were tested for speech perception three or more months
after a Nucleus 22 channels cochlear implant. The cause of deafness in nine
patients was labyrinthitis, ototoxicity in five, meningitis in three and unknown in
the remaining 34. Speech perception was measured by vowel, consonant and word
recognition using a live voice, and monosyllable, word and sentence recognition
using a videodisc. All tests were administered in a sound only condition. Results
of the univariate analysis indicated that age at implantation was correlated with
monosyllable recognition, and duration of deafness was correlated with live voice
word recognition. Residual hearing and coding strategy were both correlated with
all outcome measures. The multivariate analysis revealed that coding strategy,
duration of deafness, residual hearing and the number of electrodes were
significant predictors of live voice word recognition in that order.
92. Kawashima, T.; Iwaki, T.; Yamamoto, K.; Doi, K.; Kudo, T. [Predictive factors for
speech perception in patients with cochlear implant]. Nippon-Jibiinkoka-Gakkai-
Kaiho. 1998 Jun; 101(6): 829-35; ISSN: 0030-6622.
JAPAN. Cochlear implant therapy is an epoch-making advance in artificial
sensory organ transplants, but the positive effects on speech perception vary.
Quantification theory type I, a multivariate analysis, was used to determine
predictive factors for speech perception in patients with cochlear implants. Fifty-
one postlingual deaf adults (18 male and 33 female, mean age, 53.4, mean duration
of deafness, 8.6 years) were tested for speech perception three or more months
after a Nucleus 22 channels cochlear implant. The cause of deafness in nine
patients was labyrinthitis, ototoxicity in five, meningitis in three and unknown in
the remaining 34. Speech perception was measured by vowel, consonant and word
recognition using a live voice, and monosyllable, word and sentence recognition
using a videodisc. All tests were administered in a sound only condition. Results
of the univariate analysis indicated that age at implantation was correlated with
monosyllable recognition, and duration of deafness was correlated with live voice
word recognition. Residual hearing and coding strategy were both correlated with
all outcome measures. The multivariate analysis revealed that coding strategy,
duration of deafness, residual hearing and the number of electrodes were
significant predictors of live voice word recognition in that order.
93. Kim, J. S.; Im, J. H.; Kwon, S. U.; Kang, J. H.; Lee, M. C. Micrographia after
thalamo-mesencephalic infarction: evidence of striatal dopaminergic hypofunction.
Neurology. 1998 Aug; 51(2): 625-7; ISSN: 0028-3878.
UNITED-STATES. A patient with left thalamo-mesencephalic infarction
presented with micrographia in the right hand as the only motor sign. Brain MRI
and 99mTc ethyl cysteinate dimer (ECD) perfusion SPECT revealed ischemic
lesions in the left midbrain and the anterior thalamus, but not in the basal ganglia,
whereas [123I]-IPT SPECT demonstrated decreased activity of the [123I]-IPT in
the left striatum. The patient's micrographia may be related to a dysfunctional
nigrostriatal dopaminergic system secondary to ischemic damage to the substantia
nigra.. 51-61-6.
94. Kim, Y. S.; Joo, W. S.; Jin, B. K.; Cho, Y. H.; Baik, H. H.; Park, C. W. Melatonin
protects 6-OHDA-induced neuronal death of nigrostriatal dopaminergic system.
Neuroreport. 1998 Jul 13; 9(10): 2387-90; ISSN: 0959-4965.
ENGLAND. In vivo neuroprotective effects of melatonin on the nigrostriatal
dopaminergic system in rats unilateral 6-hydroxydopamine (6-OHDA) lesions
were tested. Two weeks after lesioning the dopamine receptor agonist,
apomorphine produced rotational asymmetry. In contrast, melatonin treatment
significantly reduced the motor deficit following apomorphine challenge. Analysis
by tyrosine hydroxylase (TH) immunocytochemistry revealed the loss of cell
bodies in the substantia nigra (SN) and absence of terminals in the dorsolateral
striatum ipsilaterally. Melatonin treatment also resulted in the survival of
dopaminergic neurons in SN and TH-immuoreactive terminals in the dorsolateral
striatum. These behavioral and histochemical results may indicate a
neuroprotective action of melatonin and suggest a potential pharmacological role
in the treatment of Parkinson's disease.. EC 1.14.16.2; 0; 0; 0; 1199-18-4; 51-61-
6; 73-31-4.
95. Kimmel, H. L.; Justice, JB Jr; Holtzman, S. G. Dissociation of morphine-induced
potentiation of turning and striatal dopamine release by amphetamine in the
nigrally-lesioned rat. Eur-J-Pharmacol. 1998 Apr 10; 346(2-3): 203-8; ISSN:
0014-2999.
NETHERLANDS. Morphine has been reported to increase extracellular levels of
dopamine in the brain of intact rats and to potentiate turning induced by
amphetamine in nigrally-lesioned rats. The present study tested the hypothesis
that there is a causal relationship between these two effects of morphine. We
tested morphine alone, amphetamine alone, and the combination in separate
groups of nigrally-lesioned rats for effects on turning and, by microdialysis, on
extracellular dopamine levels. Morphine (3.0 or 10 mg/kg) did not produce
significant turning but amphetamine (1.0 mg/kg) did. The lower dose, but not the
higher dose, of morphine potentiated amphetamine-induced turning.
Amphetamine, but not morphine, produced increases in extracellular dopamine
levels. In contrast to what occurred with turning, 10 mg/kg but not 3.0 mg/kg
morphine potentiated amphetamine-induced increases in extracellular dopamine
levels. These results show that the potentiation of amphetamine-induced turning
by morphine in nigrally-lesioned rats is not due to the potentiation of dopamine
release in the intact striatum.. 0; 0; 0; 0; 300-62-9; 51-61-6; 57-27-2.
96. Kirik, D.; Rosenblad, C.; Bjorklund, A. Characterization of behavioral and
neurodegenerative changes following partial lesions of the nigrostriatal dopamine
system induced by intrastriatal 6-hydroxydopamine in the rat. Exp-Neurol. 1998
Aug; 152(2): 259-77; ISSN: 0014-4886.
UNITED-STATES. Partial lesions of the nigrostriatal dopamine system have
been investigated with respect to their ability to induce consistent long-lasting
deficits in movement initiation and skilled forelimb use. In eight different lesion
groups 6-hydroxydopamine (6-OHDA) was injected at one, two, three, or four
sites into the lateral sector of the right striatum, in a total dose of 20-30
microgram. Impairments in movement initiation in a forelimb stepping test, and in
skilled paw use in a paw-reaching test, was seen only in animals where the
severity of the lesion exceeded a critical threshold, which was different for the
different tests used: single (1 x 20 microgram) or two-site (2 x 10 microgram)
injections into the striatum had only small affects on forelimb stepping, no effect
on skilled paw use. More pronounced deficits were obtained in animals where the
same total dose of 6-OHDA was distributed over three or four sites along the
rostro-caudal extent of the lateral striatum or where the injections were made close
to the junction of the globus pallidus. The results show that a 60-70% reduction
in tyrosine hydroxylase (TH)-positive fiber density in the lateral striatum,
accompanied by a 50-60% reduction in TH-positive cells in substantia nigra (SN),
is sufficient for the induction of significant impairment in initiation of stepping.
Impaired skilled paw-use, on the other hand, was obtained only with a four-site (4
x 7 microgram) lesion, which induced 80-95% reduction in TH fiber density
throughout the rostrocaudal extent of the lateral striatum and a 75% loss of TH-
positive neurons in SN. Drug-induced rotation, by contrast, was observed also in
animals with more restricted presymptomatic lesions. The results indicate that the
four-site intrastriatal 6-OHDA lesion may be a relevant model of the
neuropathology seen in parkinsonian patients in a manifest symptomatic stage of
the disease and may be particularly useful experimentally since it leaves a
significant portion of the nigrostriatal projection intact which can serve as a
substrate for regeneration and functional recovery in response to growth
promoting and neuroprotective agents. Copyright 1998 Academic Press.. EC
1.14.16.2; 1199-18-4; 300-62-9; 51-61-6; 58-00-4.
97. Kirkby, D. L.; Higgins, G. A. Characterization of perforant path lesions in rodent
models of memory and attention. Eur-J-Neurosci. 1998 Mar; 10(3): 823-38; ISSN:
0953-816X.
FRANCE. Early stage Alzheimer's disease (AD) pathology is associated with
neurodegeneration of systems within the temporal cortex, e.g. the entorhinal
cortex, perforant pathway and hippocampus. The perforant pathway provides
the major neuronal input to the hippocampus from the entorhinal cortex and thus
relays multimodal sensory information derived from cortical zones into the
hippocampus. The earliest symptoms of AD include cognitive impairments, e.g.
deficits in short-term memory and attention. Consequently, we have investigated
the effect of bilateral knife cut lesions to the perforant path on cognition in rats
using models measuring primarily short-term memory (operant delayed match to
position task), attention (serial five-choice reaction time task) and spatial learning
(Morris water maze). Rats receiving bilateral perforant path lesions showed
normal neurological function and a mild hyperactivity. The lesion produced little
effect on attention assessed using the five-choice task. In contrast, animals with
equivalent lesions showed a robust delay-dependent deficit in the delayed match
to position task. Spatial learning in the water maze task was also severely
impaired. The delay-dependent deficit in the match to position task was not
reversed by tacrine (3 mg/kg) pretreatment. The present data support a selective
impairment of cognitive function following perforant path lesions that was
confined to mnemonic rather than attentional processing. These findings
complement primate and human studies identifying a critical role of the perforant
pathway and associated temporal lobe structures in declarative memory.
Degeneration of the perforant pathway is likely to contribute to the mnemonic
deficits characteristic of early AD. The failure of tacrine to ameliorate these
deficits may be relevant to an emerging clinical literature suggesting that
cholinomimetic therapies improve attentional rather than mnemonic function in
AD.
98. Kirkby, D. L.; Higgins, G. A. Characterization of perforant path lesions in rodent
models of memory and attention. Eur-J-Neurosci. 1998 Mar; 10(3): 823-38; ISSN:
0953-816X.
FRANCE. Early stage Alzheimer's disease (AD) pathology is associated with
neurodegeneration of systems within the temporal cortex, e.g. the entorhinal
cortex, perforant pathway and hippocampus. The perforant pathway provides
the major neuronal input to the hippocampus from the entorhinal cortex and thus
relays multimodal sensory information derived from cortical zones into the
hippocampus. The earliest symptoms of AD include cognitive impairments, e.g.
deficits in short-term memory and attention. Consequently, we have investigated
the effect of bilateral knife cut lesions to the perforant path on cognition in rats
using models measuring primarily short-term memory (operant delayed match to
position task), attention (serial five-choice reaction time task) and spatial learning
(Morris water maze). Rats receiving bilateral perforant path lesions showed
normal neurological function and a mild hyperactivity. The lesion produced little
effect on attention assessed using the five-choice task. In contrast, animals with
equivalent lesions showed a robust delay-dependent deficit in the delayed match
to position task. Spatial learning in the water maze task was also severely
impaired. The delay-dependent deficit in the match to position task was not
reversed by tacrine (3 mg/kg) pretreatment. The present data support a selective
impairment of cognitive function following perforant path lesions that was
confined to mnemonic rather than attentional processing. These findings
complement primate and human studies identifying a critical role of the perforant
pathway and associated temporal lobe structures in declarative memory.
Degeneration of the perforant pathway is likely to contribute to the mnemonic
deficits characteristic of early AD. The failure of tacrine to ameliorate these
deficits may be relevant to an emerging clinical literature suggesting that
cholinomimetic therapies improve attentional rather than mnemonic function in
AD.
99. Knopfel, T.; Guatteo, E.; Bernardi, G.; Mercuri, N. B. Hyperpolarization induces a
rise in intracellular sodium concentration in dopamine cells of the substantia nigra
pars compacta. Eur-J-Neurosci. 1998 May; 10(5): 1926-9; ISSN: 0953-816X.
FRANCE. We investigated the effect of changes in membrane-voltage on
intracellular sodium concentration ([Na+]i) of dopamine-sensitive neurons of the
substantia nigra pars compacta in a slice preparation of rat mesencephalon.
Whole-cell patch-clamp techniques were combined with microfluorometric
measurements of [Na+]i using the Na+-sensitive probe, sodium-binding
benzofuran isophthalate (SBFI). Hyperpolarization of spontaneously active
dopamine neurons (recorded in current-clamp mode) caused the cessation of
action potential firing accompanied by an elevation in [Na+]i. In dopamine
neurons voltage-clamped at a holding potential of -60 mV elevations of [Na+]i
were induced by long-lasting (45-60 s) voltage jumps to more negative membrane
potentials (-90 to -120 mV) but not by corresponding voltage jumps to -30 mV.
These hyperpolarization-induced elevations of [Na+]i were depressed during
inhibition of I(h), a hyperpolarization-activated inward current, by Cs+.
Hyperpolarization-induced elevations in [Na+]i might occur also in other cell
types which express a powerful I(h) and might signal lack of postsynaptic
activity.. 51-61-6; 7440-23-5.
100. Kramer, P. J.; Caldwell, J.; Hofmann, A.; Tempel, P.; Weisse, G. Neurotoxicity risk
assessment of MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) as a
synthetic impurity of drugs. Hum-Exp-Toxicol. 1998 May; 17(5): 283-93; ISSN:
0960-3271.
ENGLAND. 1-Methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) induces
symptoms indistinguishable from those of Parkinson's disease. It selectively
destroys dopaminergic neurons in the substantia nigra and the globus pallidus.
Death of these same neurons is apparently the cause of idiopathic Parkinson's
disease. As phenyl-1,2,3,6 tetrahydropyridine is a commonly encountered
subunit in heterocyclic drugs and because MPTP was found as a minor impurity
in early batches of a candidate drug at Merck KGaA, it may be assumed that
MPTP will also be present as an as yet undiscovered minor impurity in various
existing drugs. A neurotoxicity risk assessment on MPTP has been conducted to
define the risk of MPTP as an impurity in drugs that are used orally. This risk
assessment has shown that compounds containing less than 5.0 p.p.m. MPTP
administered orally will not cause a neurotoxicological health risk to patients
treated with such a drug.. 0; 28289-54-5.
101. Lanca, A. J.; De Cabo, C.; Arifuzzaman, A. I.; Vaccarino, F. J. Cholecystokinergic
innervation of nucleus accumbens subregions. Peptides. 1998; 19(5): 859-68;
ISSN: 0196-9781.
UNITED-STATES. Behavioral and pharmacological evidence has shown a
different and opposite role of the neuropeptide cholecystokinin (CCK) on the
dopamine (DA) function in the caudal versus rostral part of the nucleus
accumbens. Previous reports have speculated that the caudal region of the nucleus
accumbens would receive CCKergic innervation from dopaminergic neurons of the
mesencephalic ventral tegmental area, whereas the CCKergic input to the rostral
accumbens would originate in non-dopaminergic neurons from extra-
mesencephalic areas of the brain. In the present study, this issue was addressed
using retrograde tracing techniques in conjunction with immunocytochemistry.
Retrograde tracers were injected in the three compartments of the accumbens (i.e.,
rostral pole, core and septal shell). In summary, our results demonstrate that 1)
the main CCKergic input of the accumbens originates in the ventral
mesencephalon; 2) the rostral pole is equally innervated by CCK neurons
projecting from both substantia nigra pars compacta and ventral tegmental area; 3)
the primary source of CCK innervation of the accumbal core is the substantia
nigra pars compacta; and 4) whereas the CCKergic input to the septal shell
originates primarily in the ventral tegmental area. Additionally, our results also
showed that most of the CCKergic neurons projecting to any of the accumbal
compartments also produce dopamine. These data constitute the first
neuroanatomical evidence for the differential effects of CCK on dopamine actions
in the different regions of the nucleus accumbens.. 51-61-6; 9011-97-6.
102. Laufer, Y.; Hocherman, S. Visual and kinesthetic control of goal-directed movements
to visually and kinesthetically presented targets. Percept-Mot-Skills. 1998 Jun;
86(3 Pt 2): 1375-91; ISSN: 0031-5125.
UNITED-STATES. The study investigated the contribution of kinesthetic and
visual input to the performance of reaching movements and identified rules
governing the transformation of information between these two sensory
modalities. The study examined the accuracy by which 39 subjects reproduced
locations of five targets in a horizontal plane. Mode of target presentation and
feedback during reproduction of a target's location was either visual, kinesthetic or
a combination of both modalities. Thus, it was possible to examine performance
when target presentation and reproduction involved feedback from the same
sensory modality (intramodal) as well as from different sensory modalities
(intermodal). Errors in target reproduction were calculated in terms of distance and
systematic biases in movement extent. The major findings of the study are (1)
Intramodal reproduction of a target's location on the basis of kinesthetic feedback
is somewhat less accurate than intramodal reproduction on the basis of visual
feedback (2) Intermodal performance is significantly less accurate than intramodal
performance. (3) Accuracy of performance does not depend on the direction of
information transfer between sensory modalities. (4) Intermodal performance is
characterized by systematic biases in extent of movement which are dependent on
the direction of information transfer between modalities. (5) When presentation of
the target's location is bimodal, reproduction is adversely affected by the
conflicting input. The results suggest that transformation rules, used to combine
input from various sensory modalities, depend on environmental conditions and
attention.
103. Laufer, Y.; Hocherman, S. Visual and kinesthetic control of goal-directed movements
to visually and kinesthetically presented targets. Percept-Mot-Skills. 1998 Jun;
86(3 Pt 2): 1375-91; ISSN: 0031-5125.
UNITED-STATES. The study investigated the contribution of kinesthetic and
visual input to the performance of reaching movements and identified rules
governing the transformation of information between these two sensory
modalities. The study examined the accuracy by which 39 subjects reproduced
locations of five targets in a horizontal plane. Mode of target presentation and
feedback during reproduction of a target's location was either visual, kinesthetic or
a combination of both modalities. Thus, it was possible to examine performance
when target presentation and reproduction involved feedback from the same
sensory modality (intramodal) as well as from different sensory modalities
(intermodal). Errors in target reproduction were calculated in terms of distance and
systematic biases in movement extent. The major findings of the study are (1)
Intramodal reproduction of a target's location on the basis of kinesthetic feedback
is somewhat less accurate than intramodal reproduction on the basis of visual
feedback (2) Intermodal performance is significantly less accurate than intramodal
performance. (3) Accuracy of performance does not depend on the direction of
information transfer between sensory modalities. (4) Intermodal performance is
characterized by systematic biases in extent of movement which are dependent on
the direction of information transfer between modalities. (5) When presentation of
the target's location is bimodal, reproduction is adversely affected by the
conflicting input. The results suggest that transformation rules, used to combine
input from various sensory modalities, depend on environmental conditions and
attention.
104. Levant, B. Differential distribution of D3 dopamine receptors in the brains of several
mammalian species. Brain-Res. 1998 Aug 3; 800(2): 269-74; ISSN: 0006-8993.
NETHERLANDS. The D3 dopamine receptor has been proposed as a potential
target for the treatment of schizophrenia and drug abuse. This study compares the
distribution of D3 sites in mouse, rat, guinea pig, and rabbit brain, and dog and
human cerebellum using quantitative autoradiography with the putatively
selective D3 receptor radioligand [3H]PD 128907. In the mouse, rat, guinea pig,
and rabbit, specific [3H]PD 128907 binding was heterogeneously distributed with
highest densities observed in the islands of Calleja, followed by the nucleus
accumbens. Moderate densities of [3H]PD 128907 binding were observed in the
anteroventral and dorsomedial caudate nucleus. Dense [3H]PD 128907-labelled
sites were observed in the dorsal thalamus, posterior mamilliary nucleus, and
dorsomedial interpeduncular nucleus of the rabbit that were not detected in the
other species studied. Moderately dense []PD 128907 binding was also observed
in the molecular layer of cerebellar lobule X of the rat but not in the mouse, guinea
pig, rabbit, dog, or human. These observations indicate significant inter-species
differences in the distribution of D3 receptors. Copyright 1998 Elsevier Science
B.V. All rights reserved.. 0; 0; 0; 0; 0; 10028-17-8; 123594-64-9.
105. Malchaire, J.; Rodriguez Diaz, L. S.; Piette, A.; Goncalves Amaral, F.; de Schaetzen,
D. Neurological and functional effects of short-term exposure to hand-arm
vibration. Int-Arch-Occup-Environ-Health. 1998 Jun; 71(4): 270-6; ISSN: 0340-
0131.
GERMANY. OBJECTIVE: The aim of the present study was to quantify the
sensory and functional effects resulting from a short-duration (30 min) exposure
to hand-arm vibration. SUBJECTS AND METHODS: Nine subjects went
through nine laboratory experiments. For 32 min they grasped a handle vibrating
at three different amplitudes (5, 20, and 80 ms-2) and at three frequencies (31.5,
125, and 500 Hz). Additionally, a reference experiment was conducted in which
the handle did not vibrate. Three sensory tests [vibration perception threshold
(VPT), pressure perception threshold (PPT), and distal sensory latency time
(DSL)], two functional tests [Purdue peg-board (PPB) and maximal voluntary
force (MVF)], and a questionnaire concerning the perceived paresthesia and
numbness were completed before, during, and after exposure. RESULTS: A 32-
min period of exposure to vibration leads to a temporary threshold shift (TTS) of
the VPT and to the development of paresthesia and numbness. The VPT appears
to vary with the exposure duration according to a first-order model with a time
constant about equal to 3 min. The TTS increases with the vibration acceleration
amplitude and is greater for an exposure frequency of 125 Hz than for that of 31.5
or 500 Hz. It is also greater at the test frequency 125 Hz than at 31.5 Hz. The
other tests do not demonstrate any significant variation. In particular, the PPB
test does not demonstrate any loss of dexterity. CONCLUSION: After some 30
min of exposure to vibration the VPTs are increased and paresthesia and
numbness develop. However, these do not appear to influence significantly the
capacity or performance at work.
106. Malchaire, J.; Rodriguez Diaz, L. S.; Piette, A.; Goncalves Amaral, F.; de Schaetzen,
D. Neurological and functional effects of short-term exposure to hand-arm
vibration. Int-Arch-Occup-Environ-Health. 1998 Jun; 71(4): 270-6; ISSN: 0340-
0131.
GERMANY. OBJECTIVE: The aim of the present study was to quantify the
sensory and functional effects resulting from a short-duration (30 min) exposure
to hand-arm vibration. SUBJECTS AND METHODS: Nine subjects went
through nine laboratory experiments. For 32 min they grasped a handle vibrating
at three different amplitudes (5, 20, and 80 ms-2) and at three frequencies (31.5,
125, and 500 Hz). Additionally, a reference experiment was conducted in which
the handle did not vibrate. Three sensory tests [vibration perception threshold
(VPT), pressure perception threshold (PPT), and distal sensory latency time
(DSL)], two functional tests [Purdue peg-board (PPB) and maximal voluntary
force (MVF)], and a questionnaire concerning the perceived paresthesia and
numbness were completed before, during, and after exposure. RESULTS: A 32-
min period of exposure to vibration leads to a temporary threshold shift (TTS) of
the VPT and to the development of paresthesia and numbness. The VPT appears
to vary with the exposure duration according to a first-order model with a time
constant about equal to 3 min. The TTS increases with the vibration acceleration
amplitude and is greater for an exposure frequency of 125 Hz than for that of 31.5
or 500 Hz. It is also greater at the test frequency 125 Hz than at 31.5 Hz. The
other tests do not demonstrate any significant variation. In particular, the PPB
test does not demonstrate any loss of dexterity. CONCLUSION: After some 30
min of exposure to vibration the VPTs are increased and paresthesia and
numbness develop. However, these do not appear to influence significantly the
capacity or performance at work.
107. Mathieu, Kia AM; Pages, C.; Besson, M. J. Inducibility of c-Fos protein in visuo-
motor system and limbic structures after acute and repeated administration of
nicotine in the rat. Synapse. 1998 Aug; 29(4): 343-54; ISSN: 0887-4476.
UNITED-STATES. To identify neuroanatomical substrates affected by nicotine,
we have studied its effects after acute and repeated administration through the c-
Fos protein inducibility in various brain structures. Ninety minutes after acute
nicotine (0.35 mg/kg, s.c.) the number of c-Fos-like immunoreactive nuclei was
consistently increased in visuo-motor structures such as the superior colliculus,
the medial terminal nucleus of accessory optic tract, and the nucleus of the optic
tract. The anteroventral and lateroposterior thalamic nuclei, connected with the
retina and involved in limbic processing, showed a c-Fos induction. c-Fos was
preferentially induced in terminal fields of neurons of the ventral tegmental area
such as the nucleus accumbens, the central amygdala, the lateral habenula, the
lateral septum, as well as the cingulate, medial prefrontal, orbital and piriform
cortices. In chronically treated rats (0.35 mg/kg s.c., 3 x day for 14 days), the last
nicotine injection given on the 15th day was still able to induce 90 minutes later c-
Fos protein in visuo-motor, retino-limbic, subcortical, and cortical limbic
structures. Moreover, this chronic treatment produced an additional recruitment
of c-Fos-positive nuclei in the cingulate cortex, the core and the ventral shell of the
nucleus accumbens. c-Fos induction after nicotine differs from that reported after
other addictive drugs in terms of pattern and chronic inducibility, indicating that
different mechanisms are involved for maintaining this transcription factor. In
addition to a preferential sensitivity of mesolimbic dopaminergic neurons to
nicotine, activation of visuo-limbic and limbic regions could be relevant for
understanding some context-dependent and addictive behaviors produced by
nicotine.. 0; 0; 54-11-5.
108. Mazer, J. A. How the owl resolves auditory coding ambiguity. Proc-Natl-Acad-Sci-
U-S-A. 1998 Sep 1; 95(18): 10932-7; ISSN: 0027-8424.
UNITED-STATES. The barn owl (Tyto alba) uses interaural time difference
(ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory
neurons with sharp frequency tuning act as narrow-band coincidence detectors;
such neurons respond equally well to sounds with a particular ITD and its phase
equivalents and are said to be phase ambiguous. Higher-order neurons with broad
frequency tuning are unambiguously selective for single ITDs in response to
broad-band sounds and show little or no response to phase equivalents.
Selectivity for single ITDs is thought to arise from the convergence of parallel,
narrow-band frequency channels that originate in the cochlea. ITD tuning to
variable bandwidth stimuli was measured in higher-order neurons of the owl's
inferior colliculus to examine the rules that govern the relationship between
frequency channel convergence and the resolution of phase ambiguity. Ambiguity
decreased as stimulus bandwidth increased, reaching a minimum at 2-3 kHz. Two
independent mechanisms appear to contribute to the elimination of ambiguity: one
suppressive and one facilitative. The integration of information carried by parallel,
distributed processing channels is a common theme of sensory processing that
spans both modality and species boundaries. The principles underlying the
resolution of phase ambiguity and frequency channel convergence in the owl may
have implications for other sensory systems, such as electrolocation in electric
fish and the computation of binocular disparity in the avian and mammalian visual
systems.
109. Mazer, J. A. How the owl resolves auditory coding ambiguity. Proc-Natl-Acad-Sci-
U-S-A. 1998 Sep 1; 95(18): 10932-7; ISSN: 0027-8424.
UNITED-STATES. The barn owl (Tyto alba) uses interaural time difference
(ITD) cues to localize sounds in the horizontal plane. Low-order binaural auditory
neurons with sharp frequency tuning act as narrow-band coincidence detectors;
such neurons respond equally well to sounds with a particular ITD and its phase
equivalents and are said to be phase ambiguous. Higher-order neurons with broad
frequency tuning are unambiguously selective for single ITDs in response to
broad-band sounds and show little or no response to phase equivalents.
Selectivity for single ITDs is thought to arise from the convergence of parallel,
narrow-band frequency channels that originate in the cochlea. ITD tuning to
variable bandwidth stimuli was measured in higher-order neurons of the owl's
inferior colliculus to examine the rules that govern the relationship between
frequency channel convergence and the resolution of phase ambiguity. Ambiguity
decreased as stimulus bandwidth increased, reaching a minimum at 2-3 kHz. Two
independent mechanisms appear to contribute to the elimination of ambiguity: one
suppressive and one facilitative. The integration of information carried by parallel,
distributed processing channels is a common theme of sensory processing that
spans both modality and species boundaries. The principles underlying the
resolution of phase ambiguity and frequency channel convergence in the owl may
have implications for other sensory systems, such as electrolocation in electric
fish and the computation of binocular disparity in the avian and mammalian visual
systems.
110. McFeely, WJ Jr; Antonelli, P. J.; Rodriguez, F. J.; Holmes, A. E. Somatosensory
phenomena after multichannel cochlear implantation in prelingually deaf adults.
Am-J-Otol. 1998 Jul; 19(4): 467-71; ISSN: 0192-9763.
UNITED-STATES. OBJECTIVES: Central auditory system development in
thought to be dependent on normal auditory nerve excitation. Central auditory
disorganization may differ between prelingual and postlingual deafness. One
possible clinical manifestation of such central auditory disorganization is
somatosensory perception with cochlear implant stimulation. The purpose of this
study was to investigate the incidence and characteristics of somatosensory
phenomena in prelingually and postlingually deafened adult cochlear implant
subjects. STUDY DESIGN: The study design was a retrospective analysis.
SETTING: The study was performed at an academic tertiary referral center.
PATIENTS: This study included 32 adult multichannel cochlear implant
recipients. MAIN OUTCOME MEASURES: Subjective patient reporting of
sensory perception after cochlear implant stimulation was reviewed. RESULTS:
All 10 prelingually deaf subjects noted somatosensory phenomena distant from
the implanted ear (e.g., chest, abdomen) on implant stimulation. These sensations
resolved gradually for all patients. No subject deafened after the age of 2 years
reported somatosensory perceptions. CONCLUSIONS: Somatosensory
phenomena experienced by prelingually deafened adults suggest that
disorganization of central auditory system pathways is more severe in these
individuals. Earlier auditory deprivation appears to produce greater central
auditory alterations, and perceptible crossover between somatosensory and
auditory signals may be the end result.
111. McFeely, WJ Jr; Antonelli, P. J.; Rodriguez, F. J.; Holmes, A. E. Somatosensory
phenomena after multichannel cochlear implantation in prelingually deaf adults.
Am-J-Otol. 1998 Jul; 19(4): 467-71; ISSN: 0192-9763.
UNITED-STATES. OBJECTIVES: Central auditory system development in
thought to be dependent on normal auditory nerve excitation. Central auditory
disorganization may differ between prelingual and postlingual deafness. One
possible clinical manifestation of such central auditory disorganization is
somatosensory perception with cochlear implant stimulation. The purpose of this
study was to investigate the incidence and characteristics of somatosensory
phenomena in prelingually and postlingually deafened adult cochlear implant
subjects. STUDY DESIGN: The study design was a retrospective analysis.
SETTING: The study was performed at an academic tertiary referral center.
PATIENTS: This study included 32 adult multichannel cochlear implant
recipients. MAIN OUTCOME MEASURES: Subjective patient reporting of
sensory perception after cochlear implant stimulation was reviewed. RESULTS:
All 10 prelingually deaf subjects noted somatosensory phenomena distant from
the implanted ear (e.g., chest, abdomen) on implant stimulation. These sensations
resolved gradually for all patients. No subject deafened after the age of 2 years
reported somatosensory perceptions. CONCLUSIONS: Somatosensory
phenomena experienced by prelingually deafened adults suggest that
disorganization of central auditory system pathways is more severe in these
individuals. Earlier auditory deprivation appears to produce greater central
auditory alterations, and perceptible crossover between somatosensory and
auditory signals may be the end result.
112. Meador, K. J.; Ray, P. G.; Day, L.; Ghelani, H.; Loring, D. W. Physiology of
somatosensory perception: cerebral lateralization and extinction [see comments].
Neurology. 1998 Sep; 51(3): 721-7; ISSN: 0028-3878.
Note: Comment in: Neurology 1998 Sep;51(3):666-8.
UNITED-STATES. OBJECTIVE: To demonstrate the effects of cerebral
lateralization and temporal dynamics on somatosensory perception.
BACKGROUND: We postulated that perceptual thresholds for simple
somatosensory stimuli would be less in the left than the right hand, and that a
left/right asymmetry in extinction would exist in healthy right-handed subjects
(but not in left-handed subjects). During the course of these experiments we also
examined the controversy concerning the temporal dynamics of somatosensory
perception. METHODS: A total of 126 healthy subjects (age range, 6 to 73
years) participated in the study. Effects of handedness, age, vigilance, gaze, and
temporal interval on somatosensory perception were examined in a series of
experiments. Brief electric pulses were applied to the index finger of one or both
hands. RESULTS: Perceptual thresholds are lower in the left than the right hand
of healthy right-handed subjects in a large cohort across a wide age range. Left-
handed subjects have no overall asymmetry. Even after compensation for baseline
threshold differences, single stimuli in right-handed subjects are perceived more
readily in the left than the right hand, and left-hand targets are more difficult to
mask. Leftward eye/head gaze lowers thresholds in both hands of right-handed
subjects (compared with right or straight gaze). Extinction was consistently
maximal when the mask followed the target by 50 to 100 msec. CONCLUSIONS:
The findings demonstrate clearly that left/right perceptual thresholds for simple
somatosensory stimuli are asymmetric in healthy right-handed subjects. Both
central and peripheral asymmetries exist. The central asymmetry and gaze effects
are consistent with right cerebral dominance for externally directed attention.
Access of somatosensory stimuli to conscious awareness is delayed and
particularly vulnerable to disruption at 50 to 100 msec after onset of the stimulus.
113. Meador, K. J.; Ray, P. G.; Day, L.; Ghelani, H.; Loring, D. W. Physiology of
somatosensory perception: cerebral lateralization and extinction [see comments].
Neurology. 1998 Sep; 51(3): 721-7; ISSN: 0028-3878.
Note: Comment in: Neurology 1998 Sep;51(3):666-8.
UNITED-STATES. OBJECTIVE: To demonstrate the effects of cerebral
lateralization and temporal dynamics on somatosensory perception.
BACKGROUND: We postulated that perceptual thresholds for simple
somatosensory stimuli would be less in the left than the right hand, and that a
left/right asymmetry in extinction would exist in healthy right-handed subjects
(but not in left-handed subjects). During the course of these experiments we also
examined the controversy concerning the temporal dynamics of somatosensory
perception. METHODS: A total of 126 healthy subjects (age range, 6 to 73
years) participated in the study. Effects of handedness, age, vigilance, gaze, and
temporal interval on somatosensory perception were examined in a series of
experiments. Brief electric pulses were applied to the index finger of one or both
hands. RESULTS: Perceptual thresholds are lower in the left than the right hand
of healthy right-handed subjects in a large cohort across a wide age range. Left-
handed subjects have no overall asymmetry. Even after compensation for baseline
threshold differences, single stimuli in right-handed subjects are perceived more
readily in the left than the right hand, and left-hand targets are more difficult to
mask. Leftward eye/head gaze lowers thresholds in both hands of right-handed
subjects (compared with right or straight gaze). Extinction was consistently
maximal when the mask followed the target by 50 to 100 msec. CONCLUSIONS:
The findings demonstrate clearly that left/right perceptual thresholds for simple
somatosensory stimuli are asymmetric in healthy right-handed subjects. Both
central and peripheral asymmetries exist. The central asymmetry and gaze effects
are consistent with right cerebral dominance for externally directed attention.
Access of somatosensory stimuli to conscious awareness is delayed and
particularly vulnerable to disruption at 50 to 100 msec after onset of the stimulus.
114. Melamed, E.; Offen, D.; Shirvan, A.; Djaldetti, R.; Barzilai, A.; Ziv, I. Levodopa
toxicity and apoptosis. Ann-Neurol. 1998 Sep; 44(3 Suppl 1): S149-54; ISSN:
0364-5134.
UNITED-STATES. Many in vitro studies have shown that levodopa is a potent
toxin which is lethal to various cultured neuronal and non-neuronal cells. The in
vitro toxicity of levodopa is linked mainly to its auto-oxidation, which generates a
variety of harmful free radical species including superoxide, hydrogen peroxide,
and hydroxyl radicals, and also semiquinones and quinones produced via the
dopa-melanin metabolic route. Such toxic effects of levodopa can be blocked by
co-treatment with antioxidants, particularly thiol-containing compounds. Several
studies have shown that levodopa kills cells by triggering apoptosis, an active,
intrinsic cell suicide program. Exposure of cultured neurons to levodopa induced
the characteristic apoptotic cascade, including cell shrinkage, membrane blebbing,
and nuclear and DNA fragmentation. Although levodopa is extremely toxic in
vitro, there is no evidence that it damages nigrostriatal dopaminergic neurons in
vivo in experimental animals and in patients with Parkinson's disease (PD).
Likewise, although there is some evidence for the occurrence of apoptosis in the
parkinsonian substantia nigra, it is not known whether levodopa administration is
capable of inducing or accelerating programmed cell death of residual pigmented
nigral neurons in PD.. 0; 0; 0.
115. Millan, M. J.; Gobert, A.; Newman Tancredi, A.; Audinot, V.; Lejeune, F.; Rivet, J.
M.; Cussac, D.; Nicolas, J. P.; Muller, O.; Lavielle, G. S 16924 ((R)-2-[1-[2-(2,3-
dihydro-benzo[1,4] dioxin-5-Yloxy)-ethyl]-pyrrolidin-3yl]-1-(4-fluoro-phenyl)-
ethanone), a novel, potential antipsychotic with marked serotonin (5-HT)1A
agonist properties: I. Receptorial and neurochemical profile in comparison with
clozapine and haloperidol. J-Pharmacol-Exp-Ther. 1998 Sep; 286(3): 1341-55;
ISSN: 0022-3565.
UNITED-STATES. S 16924 showed a pattern of interaction at multiple (>20)
native, rodent and cloned, human (h) monoaminergic receptors similar to that of
clozapine and different to that of haloperidol. Notably, like clozapine, the affinity
of S 16924 for hD2 and hD3 receptors was modest, and it showed 5-fold higher
affinity for hD4 receptors. At each of these sites, using a [35S]GTPgammaS
binding procedure, S 16924, clozapine and haloperidol behaved as antagonists. In
distinction to haloperidol, S 16924 shared the marked affinity of clozapine for h5-
HT2A and h5-HT2C receptors. However, an important difference to clozapine
(and haloperidol) was the high affinity of S 16924 for h5-HT1A receptors. At
these sites, using a [35S]GTPgammaS binding model, both S 16924 and clozapine
behaved as partial agonists, whereas haloperidol was inactive. In vivo, the agonist
properties of S 16924 at 5-HT1A autoreceptors were revealed by its ability to
potently inhibit the firing of raphe-localized serotoninergic neurones, an action
reversed by the selective 5-HT1A receptor antagonist, WAY 100,635. In contrast,
clozapine and haloperidol only weakly inhibited raphe firing, and their actions
were resistant to WAY 100,635. Similarly, S 16924 more potently inhibited
striatal turnover of 5-HT than either clozapine or haloperidol. Reflecting its
modest affinity for D2 (and D3) autoreceptors, S 16924 only weakly blocked the
inhibitory influence of the dopaminergic agonist, apomorphine, upon the firing
rate of ventrotegmental area-localized dopaminergic neurones. Further, S 16924
only weakly increased striatal, mesolimbic and mesocortical turnover of dopamine
(DA). Clozapine was, similarly, weakly active in these models, whereas
haloperidol, in line with its higher affinity at D2 (and D3) receptors, was potently
active. In the frontal cortex (FCX) of freely moving rats, S 16924 dose-
dependently reduced dialysate levels of 5-HT, whereas those of DA and NAD
were dose-dependently increased in the same samples. In contrast, although S
16924 also suppressed 5-HT levels in the striatum and nucleus accumbens, DA
levels therein were unaffected. Clozapine mimicked this selective increase in DA
levels in the FCX as compared to striatum and accumbens. In contrast,
haloperidol modestly increased DA levels in the FCX, striatum and accumbens to
the same extent. In distinction to S 16924, clozapine and haloperidol exerted little
influence upon 5-HT levels. Finally, the influence of S 16924 upon FCX levels of
5-HT, DA (and NAD) was attenuated by WAY 100,635. In conclusion, S 16924
possesses a profile of interaction at multiple monoaminergic receptors comparable
to that of clozapine and distinct to that of haloperidol. In addition, S 16924 is a
potent, partial agonist at 5-HT1A receptors. Correspondingly, acute
administration of S 16924 decreases cerebral serotoninergic transmission and
selectively reinforces frontocortical as compared to subcortical dopaminergic
transmission. In line with these actions, S 16924 shows a distinctive profile of
activity in functional (behavioral) models of potential antipsychotic activity
(companion paper).. 0; 0; 0; 0; 0; 0; 112692-38-3; 37589-80-3; 50-67-9; 51-61-6;
52-86-8; 5786-21-0.
116. Mitsumoto, Y.; Watanabe, A.; Mori, A.; Koga, N. Spontaneous regeneration of
nigrostriatal dopaminergic neurons in MPTP-treated C57BL/6 mice. Biochem-
Biophys-Res-Commun. 1998 Jul 30; 248(3): 660-3; ISSN: 0006-291X.
UNITED-STATES. The spontaneous recovery of nigrostriatal dopaminergic
neurons was quantitatively analyzed with tyrosine hydroxylase (TH)-
immunocytochemistry in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
(MPTP)-treated C57BL/6 young mice. A substantial reduction of striatal
dopamine (DA) level was observed until 24 days following MPTP treatment. The
TH-immunoreactive (IR) fibers and number of TH-positive cell bodies were also
markedly reduced at 3 days after the toxin treatment. Thereafter, TH-IR fiber
densities showed to progressively recover through the examining period. The
number of TH-positive cell bodies in substantia nigra pars compacta were not
changed during the recovery period. These results indicate that MPTP-treated
mice have a potential for spontaneous regenerative sprouting in nigrostriatal
dopaminergic system.. EC 1.14.16.2; 102-32-9; 28289-54-5; 306-08-1; 51-61-6.
117. Mohanakumar, K. P.; Hanbauer, I.; Chiueh, C. C. Neuroprotection by nitric oxide
against hydroxyl radical-induced nigral neurotoxicity. J-Chem-Neuroanat. 1998
Jun; 14(3-4): 195-205; ISSN: 0891-0618.
NETHERLANDS. We investigated the effects of nitric oxide on an in vitro and in
vivo generation of hydroxyl radicals, and in vivo neurotoxicity caused by
intranigral infusion of ferrous citrate in rats. The formation of hydroxyl radicals in
vitro, without exogenous hydrogen peroxide, was dose-dependent. Some nitric
oxide donors (e.g. sodium nitroprusside) stimulated, while others (nitroglycerin,
diethylamine/nitric oxide, nitric oxide in Ringer's solution) suppressed hydroxyl
radical generation in vitro. A significant increase in extra-cellular hydroxyl radicals
was detected in a brain microdialysis study. Intranigral infusion of ferrous citrate
caused long-lasting lipid peroxidation and dopamine depletion in the ipsilateral
nigral region and striatum, respectively. Sub-acute dopamine depletion in the
striatum was positively correlated with acute lipid peroxidation in substantia
nigra. Intranigral administration of nitric oxide did not affect striatal dopamine.
Interestingly, nitric oxide in Ringer's protected nigral neurones against the
oxidative injury. The results demonstrate that a regional increase in the levels of
iron can result in hydroxyl radical generation and lipid peroxidation leading to
neurotoxicity. It also demonstrates that exogenous nitric oxide can act as hydroxyl
radical scavenger and protect neurones from oxidative injury.. 0; 0; 10102-43-9;
23383-11-1; 3352-57-6; 51-61-6.
118. Mohanty, S.; Steinbusch, H. W.; Ganguly, D. K.; Mohanakumar, K. P. Behavioral
and neurochemical alterations following intracerebroventricular administration of
anti-serotonin antibodies in adult Balb/c mice. J-Chem-Neuroanat. 1998 Jun; 14(3-
4): 141-9; ISSN: 0891-0618.
NETHERLANDS. The effects of intracerebroventricular injections of serotonin
(5-HT) antibodies were studied for changes in 5-HT, dopamine (DA), their
metabolites and norepinephrine (NE) as well as 5-HT mediated behavior in adult
mice. While nociceptive thresholds (tail-flick latency) were inhibited in antibody
treated animals, tremor response to 5-methoxy-N,N-dimethyl tryptamine
administration was increased. 5-HT and DA in the nucleus raphe dorsalis (NRD),
substantia nigra (SN), nucleus caudatus putamen (NCP) and in the substantia
grisea centralis, and NE in the former two nuclei were significantly decreased in
these animals. 5-Hydroxyindoleacetic acid was unaffected in all nuclei except
NRD, where it was inhibited. Homovanillic acid and 3,4-dihydroxyphenylacetic
acid were inhibited in all nuclei except in NCP. The brunt of insult was more
evident in NRD and SN where all neurotransmitters were inhibited for a longer
period. 5-HT turnover was increased in all the nuclei, however only SN showed
increased DA turnover. It may be assumed that the observed neurochemical and
behavioral changes were the consequence of the antibodies binding to 5-HT, which
in turn influenced the anatomically and functionally connected neurotransmitters.
While the study contributes to the existing understanding of central
neurotransmitter control on behavior, it fails to delineate the underlying
mechanism. The possibility of developing a useful, drug-free 5-HT deficient
animal model for studying clinical disorders, as well as for solving some of the
basic questions related to the physiological functions of 5-HT in adult animals are
envisaged from the study.. 0; 50-67-9; 51-41-2; 51-61-6.
119. Moore, C. M.; Egeth, H. How does feature-based attention affect visual processing?
J-Exp-Psychol-Hum-Percept-Perform. 1998 Aug; 24(4): 1296-310; ISSN: 0096-
1523.
UNITED-STATES. Five experiments are reported from which it is concluded
that attending on the basis of a stimulus feature (e.g., red) does not directly affect
the sensory quality of stimuli that possess that feature. Feature-based attention
was manipulated in a visual search task by providing information about the
probability that the target would possess a given feature (e.g., "The target has a
1.0 probability of being red when present.") Feature-based attention failed to aid
performance under "data-limited" conditions (i.e., those under which performance
was primarily affected by the quality of the stimulus) but did affect performance
under conditions that were not data limited (Experiments 1-3). If attending to a
feature had affected the sensory quality of stimuli, performance should have been
aided under all conditions. Experiments 4 and 5 provided converging support for
this conclusion.
120. Moore, C. M.; Egeth, H. How does feature-based attention affect visual processing?
J-Exp-Psychol-Hum-Percept-Perform. 1998 Aug; 24(4): 1296-310; ISSN: 0096-
1523.
UNITED-STATES. Five experiments are reported from which it is concluded
that attending on the basis of a stimulus feature (e.g., red) does not directly affect
the sensory quality of stimuli that possess that feature. Feature-based attention
was manipulated in a visual search task by providing information about the
probability that the target would possess a given feature (e.g., "The target has a
1.0 probability of being red when present.") Feature-based attention failed to aid
performance under "data-limited" conditions (i.e., those under which performance
was primarily affected by the quality of the stimulus) but did affect performance
under conditions that were not data limited (Experiments 1-3). If attending to a
feature had affected the sensory quality of stimuli, performance should have been
aided under all conditions. Experiments 4 and 5 provided converging support for
this conclusion.
121. Moore, R. J.; Vinsant, S. L.; Nader, M. A.; Porrino, L. J.; Friedman, D. P. Effect of
cocaine self-administration on dopamine D2 receptors in rhesus monkeys.
Synapse. 1998 Sep; 30(1): 88-96; ISSN: 0887-4476.
UNITED-STATES. The present study used autoradiography to examine the
effects of chronic self-administration of cocaine on the density of dopamine D2
receptors in nonhuman primates. Three rhesus monkeys intravenously self-
administered an average of 1.35 mg/kg cocaine per day for 18-22 months until
they were euthanized immediately after a self-administration session. Binding site
density of the D2 ligand [3H]raclopride (2 nM) was assessed in these monkeys as
well as three untreated controls, using quantitative in vitro receptor
autoradiography. As compared to untreated controls, D2 binding site density was
significantly lower in the animals that self-administered cocaine in all regions of
the striatum rostral to the anterior commissure. These regions include the anterior
and central regions of the caudate nucleus, putamen, olfactory tubercle, and both
the shell and core of the nucleus accumbens. Within the substantia nigra and
ventral tegmental area, by contrast, no differences were found in the density of D2
binding sites. These findings suggest a pervasive effect of cocaine on the regulation
of D2 receptors in the striatum. The lack of change within the ventral midbrain,
however, suggests a differential regulation of D2 receptors in the striatum and
ventral midbrain. This study confirms and extends our knowledge of the
neurobiological changes in the mesolimbic dopamine system that result from
chronic exposure to cocaine.. 0; 0; 10028-17-8; 50-36-2; 84225-95-6.
122. Moore, R. J.; Vinsant, S. L.; Nader, M. A.; Porrino, L. J.; Friedman, D. P. Effect of
cocaine self-administration on dopamine D2 receptors in rhesus monkeys.
Synapse. 1998 Sep; 30(1): 88-96; ISSN: 0887-4476.
UNITED-STATES. The present study used autoradiography to examine the
effects of chronic self-administration of cocaine on the density of dopamine D2
receptors in nonhuman primates. Three rhesus monkeys intravenously self-
administered an average of 1.35 mg/kg cocaine per day for 18-22 months until
they were euthanized immediately after a self-administration session. Binding site
density of the D2 ligand [3H]raclopride (2 nM) was assessed in these monkeys as
well as three untreated controls, using quantitative in vitro receptor
autoradiography. As compared to untreated controls, D2 binding site density was
significantly lower in the animals that self-administered cocaine in all regions of
the striatum rostral to the anterior commissure. These regions include the anterior
and central regions of the caudate nucleus, putamen, olfactory tubercle, and both
the shell and core of the nucleus accumbens. Within the substantia nigra and
ventral tegmental area, by contrast, no differences were found in the density of D2
binding sites. These findings suggest a pervasive effect of cocaine on the regulation
of D2 receptors in the striatum. The lack of change within the ventral midbrain,
however, suggests a differential regulation of D2 receptors in the striatum and
ventral midbrain. This study confirms and extends our knowledge of the
neurobiological changes in the mesolimbic dopamine system that result from
chronic exposure to cocaine.. 0; 0; 10028-17-8; 50-36-2; 84225-95-6.
123. Morgan, J.; Roufeil, L.; Kaushik, S.; Bassett, M. Influence of coping style and
precolonoscopy information on pain and anxiety of colonoscopy. Gastrointest-
Endosc. 1998 Aug; 48(2): 119-27; ISSN: 0016-5107.
UNITED-STATES. BACKGROUND: This study assessed the relationship
between patient coping style, precolonoscopy information, and anxiety and pain
associated with colonoscopy. METHODS: Eighty consecutive adult patients
undergoing initial colonoscopy were classified into two groups on the basis of
coping style: information seekers or information avoiders. All were given
standardized information about colonoscopy. Half of each group was randomly
assigned to receive additional sensory information describing what they could
expect to feel. Self-report, physiologic, and behavioral indices of anxiety and pain
were measured. RESULTS: Patients given information congruent with coping
style experienced significantly less self-report anxiety immediately after the
information intervention and spent less time in recovery. In contrast, patients
given information not congruent with coping style maintained their pre-
intervention anxiety level. Patients given information congruent with coping style
scored lower on behavioral indices of pain, but there were no differences with
respect to patient perception of pain or the dosage of sedative drugs. Most
patients reported that the bowel preparation was the most distressing part of the
colonoscopy. CONCLUSIONS: Assessment of coping style and provision of
congruent information reduces anxiety, recovery time, and observed behavioral
indices of pain of colonoscopy but has no effect on sedation dose or patient
perception of pain.
124. Morgan, J.; Roufeil, L.; Kaushik, S.; Bassett, M. Influence of coping style and
precolonoscopy information on pain and anxiety of colonoscopy. Gastrointest-
Endosc. 1998 Aug; 48(2): 119-27; ISSN: 0016-5107.
UNITED-STATES. BACKGROUND: This study assessed the relationship
between patient coping style, precolonoscopy information, and anxiety and pain
associated with colonoscopy. METHODS: Eighty consecutive adult patients
undergoing initial colonoscopy were classified into two groups on the basis of
coping style: information seekers or information avoiders. All were given
standardized information about colonoscopy. Half of each group was randomly
assigned to receive additional sensory information describing what they could
expect to feel. Self-report, physiologic, and behavioral indices of anxiety and pain
were measured. RESULTS: Patients given information congruent with coping
style experienced significantly less self-report anxiety immediately after the
information intervention and spent less time in recovery. In contrast, patients
given information not congruent with coping style maintained their pre-
intervention anxiety level. Patients given information congruent with coping style
scored lower on behavioral indices of pain, but there were no differences with
respect to patient perception of pain or the dosage of sedative drugs. Most
patients reported that the bowel preparation was the most distressing part of the
colonoscopy. CONCLUSIONS: Assessment of coping style and provision of
congruent information reduces anxiety, recovery time, and observed behavioral
indices of pain of colonoscopy but has no effect on sedation dose or patient
perception of pain.
125. Morzorati, S. L. VTA dopamine neuron activity distinguishes alcohol-preferring (P)
rats from Wistar rats. Alcohol-Clin-Exp-Res. 1998 Jun; 22(4): 854-7; ISSN: 0145-
6008.
UNITED-STATES. The mesolimbic dopamine (DA) system is innately deficient
in rats selectively bred for high alcohol drinking behavior compared with rats
selectively bred for low alcohol drinking and unselected rats. In alcohol-preferring
(P) rats, compared with alcohol-nonpreferring (NP) rats, this is evidenced by
fewer DA neurons in the ventral tegmental area (VTA) projecting to the nucleus
accumbens (ACB). Yet, despite this deficiency, DA release in the ACB is similar
in P, NP, and Wistar rats. DA release is regulated by DA neuronal activity, and
DA neurons fire tonically as well as in bursts. Burst firing has been shown to
substantially enhance DA release compared with tonic firing. The present study
was designed to test the hypothesis that the remaining VTA DA neurons in P rats
have faster firing frequencies and/or burst fire more frequently than VTA DA
neurons in Wistar rats. The spontaneous activity of VTA DA neurons was
recorded in unanesthetized alcohol-naive P and Wistar rats. A conventional burst
analysis on 500 consecutive action potentials revealed that P rats had a
significantly (p < 0.05) greater percentage of action potentials in bursts when
compared with Wistar rats (P: 50.9%, Wistar: 34.4%). Firing frequency and other
burst parameters (burst interspike interval, burst length, interburst interval, and
the number of action potentials per burst) did not distinguish the two groups of
rats. The increased burst activity in P rats may represent a compensatory
mechanism to maintain adequate basal levels of DA despite the deficiency in the
mesolimbic DA system.. 51-61-6.
126. Murai, T.; Yoshida, Y.; Koide, S.; Takada, K.; Misaki, T.; Koshikawa, N.; Cools, A.
R. Clonidine reduces dopamine and increases GABA in the nucleus accumbens: an
in vivo microdialysis study. Pharmacol-Biochem-Behav. 1998 Jul; 60(3): 695-701;
ISSN: 0091-3057.
UNITED-STATES. The effects of clonidine, an alpha2 adrenoceptor agonist, on
extracellular concentrations of dopamine and gamma-aminobutyric acid (GABA)
in the nucleus accumbens of rats were studied by using in vivo brain
microdialysis. Clonidine (5 microg/kg i.v.) significantly decreased the brain
microdialysate concentration of dopamine in the nucleus accumbens up to a
maximum of 16% at its peak effect. This effect was inhibited by a dose of
idazoxan (10 microg/kg i.v.), an alpha2-adrenoceptor antagonist. which itself did
not affect the efflux of dopamine. A smaller dose of clonidine (1 microg/kg i.v.),
which had no significant effect on dopamine efflux per se, decreased the dopamine
efflux (21% reduction) when given together with an ineffective dose of midazolam
(0.075 mg/kg i.v.), a benzodiazepine receptor agonist. The effect of clonidine (5
microg/kg i.v.) on mesolimbic dopamine efflux was abolished by bicuculline (1
mg/kg i.v.), a GABA(A) receptor antagonist, counteracted by beta-carboline-3-
carboxylate ethyl ester (beta-CCE, 3 mg/kg i.p.), a benzodiazepine receptor
inverse agonist, but not affected by flumazenil (6 microg/kg i.v.), a benzodiazepine
receptor antagonist. Clonidine (5 microg/kg i.v.) increased the dialysate
concentration of GABA in the nucleus accumbens up to a maximum of 250% at
its peak effect, but not in the ventral tegmental area. It is hypothesized that
GABA(A) binding sites in the nucleus accumbens form part of the sequence of
events that is triggered by clonidine in an alpha2-adrenergic-specific manner and
that ultimately results in a decreased release of dopamine in the nucleus
accumbens.. 0; 0; 0; 0; 4205-90-7; 51-61-6; 56-12-2; 79944-58-4.
127. Nicol, A. U.; Brown, M. W.; Horn, G. Neural encoding of subject-object distance in a
visual recognition system. Eur-J-Neurosci. 1998 Jan; 10(1): 34-44; ISSN: 0953-
816X.
FRANCE. Domestic chicks follow a familiar (imprinted) object when it recedes.
In behaving, imprinted chicks with no experience of objects at different distances,
neuronal activity was recorded from the intermediate and medial part of the
hyperstriatum ventrale (IMHV), a brain region crucial for the recognition memory
underlying imprinting. We found that (i) some neurones responded equivalently,
irrespective of the subject-object distance d (d-invariant); (ii) other neurones
responded differently at different values of d (d-sensitive); (iii) these response
types were found in monocular chicks and in chicks with both eyes exposed; (iv)
the action potential shape of d-invariant neurones was different from that of other
neurones and (v) the spontaneous firing rate of some neurones was correlated with
locomotor activity. Taken together with previous findings, the results raise the
possibility that IMHV has a major role to play in the sensory and motor-control
aspects of imprinting in addition to its mnemonic functions.
128. Nicol, A. U.; Brown, M. W.; Horn, G. Neural encoding of subject-object distance in a
visual recognition system. Eur-J-Neurosci. 1998 Jan; 10(1): 34-44; ISSN: 0953-
816X.
FRANCE. Domestic chicks follow a familiar (imprinted) object when it recedes.
In behaving, imprinted chicks with no experience of objects at different distances,
neuronal activity was recorded from the intermediate and medial part of the
hyperstriatum ventrale (IMHV), a brain region crucial for the recognition memory
underlying imprinting. We found that (i) some neurones responded equivalently,
irrespective of the subject-object distance d (d-invariant); (ii) other neurones
responded differently at different values of d (d-sensitive); (iii) these response
types were found in monocular chicks and in chicks with both eyes exposed; (iv)
the action potential shape of d-invariant neurones was different from that of other
neurones and (v) the spontaneous firing rate of some neurones was correlated with
locomotor activity. Taken together with previous findings, the results raise the
possibility that IMHV has a major role to play in the sensory and motor-control
aspects of imprinting in addition to its mnemonic functions.
129. Nikkhah, G.; Rosenthal, C.; Falkenstein, G.; Samii, M. Dopaminergic graft-induced
long-term recovery of complex sensorimotor behaviors in a rat model of
Parkinson's disease. Zentralbl-Neurochir. 1998; 59(2): 97-103; ISSN: 0044-4251.
GERMANY. Transplantation of embryonic dopamine neurons has evolved as an
alternative neurosurgical treatment strategy for patients with Parkinson's disease
and it is therefore of great interest to further optimise this procedure in
experimental studies. We have applied a modified microtransplantation approach
in unilaterally 6-hydroxydopamine lesioned rats and observed a substantial and
long-lasting functional recovery in complex spontaneous behaviors, such as skilled
forelimb use and stepping behavior. The results demonstrate that the rat model of
Parkinson's disease is a highly useful tool to study mechanisms of neural
plasticity and regeneration. The ability of dopaminergic grafts to restore complex
sensorimotor behaviors in animals also indicate their great potential for the
development of a successful clinical application.. 1199-18-4; 51-61-6.
130. Obst, K.; Bronzel, M.; Wahle, P. Visual activity is required to maintain the
phenotype of supragranular NPY neurons in rat area 17. Eur-J-Neurosci. 1998
Apr; 10(4): 1422-8; ISSN: 0953-816X.
FRANCE. Visual activity governs the functional maturation of the mammalian
visual cortex. We report here, that visual experience is required for stabilizing the
phenotype of a subset of cortical interneurons. Neurons expressing neuropeptide
Y mRNA (NPY neurons) display a transiently higher expression in the early
postnatal visual areas 18a and 17 that is followed by a phenotype restriction
during the second postnatal month: about 50% of the NPY neurons in
supragranular and infragranular layers of area 18a, and in infragranular layers of
area 17 gradually stop the NPY expression. In contrast, the expression remains
unchanged in supragranular layers of area 17. Dark rearing rats from birth to up to
100 days does neither prevent the developmental onset of NPY mRNA
expression, nor does it prevent the phenotype restriction from occurring. In
contrast, in dark reared animals NPY neurons in supragranular layers of area 17
now also undergo a phenotype restriction. Returning animals to light after variable
periods of darkness results in an upregulation of NPY mRNA expression
selectively in neurons in supragranular layers of area 17. These neurons acquire a
constitutive expression during the second postnatal month. This suggests that the
phenotypic specification of a distinct subset of cortical interneurons is regulated
by visual experience which thus influences on the maturation of the neurochemical
architecture of area 17.. 0.
131. Obst, K.; Bronzel, M.; Wahle, P. Visual activity is required to maintain the
phenotype of supragranular NPY neurons in rat area 17. Eur-J-Neurosci. 1998
Apr; 10(4): 1422-8; ISSN: 0953-816X.
FRANCE. Visual activity governs the functional maturation of the mammalian
visual cortex. We report here, that visual experience is required for stabilizing the
phenotype of a subset of cortical interneurons. Neurons expressing neuropeptide
Y mRNA (NPY neurons) display a transiently higher expression in the early
postnatal visual areas 18a and 17 that is followed by a phenotype restriction
during the second postnatal month: about 50% of the NPY neurons in
supragranular and infragranular layers of area 18a, and in infragranular layers of
area 17 gradually stop the NPY expression. In contrast, the expression remains
unchanged in supragranular layers of area 17. Dark rearing rats from birth to up to
100 days does neither prevent the developmental onset of NPY mRNA
expression, nor does it prevent the phenotype restriction from occurring. In
contrast, in dark reared animals NPY neurons in supragranular layers of area 17
now also undergo a phenotype restriction. Returning animals to light after variable
periods of darkness results in an upregulation of NPY mRNA expression
selectively in neurons in supragranular layers of area 17. These neurons acquire a
constitutive expression during the second postnatal month. This suggests that the
phenotypic specification of a distinct subset of cortical interneurons is regulated
by visual experience which thus influences on the maturation of the neurochemical
architecture of area 17.. 0.
132. Patel, R. S.; Rao, S. S. Biomechanical and sensory parameters of the human esophagus
at four levels. Am-J-Physiol. 1998 Aug; 275(2 Pt 1): G187-91; ISSN: 0002-9513.
UNITED-STATES. The biomechanical and sensory characteristics of the lower
esophageal sphincter (LES) and those of the striated and smooth muscle portions
of the esophagus have not been compared in humans. Our aim was to determine
sensory perception, cross-sectional area (CSA), and biomechanical parameters at
different levels of the esophagus. We studied 11 healthy volunteers, using
impedance planimetry. Intermittent balloon distensions (5-60 cmH2O) were
performed at four sites: 1) the LES, 2) 5 cm above LES (distal), 3) 10 cm above
LES (mid), and 4) 5 cm below the upper esophageal sphincter (proximal). During
these distensions, CSAs, biomechanical parameters, and sensory responses were
measured. The mid-esophagus had a higher (P < 0.05) CSA than the distal
esophagus. The LES had the smallest CSA (P < 0.05). The LES and the proximal
esophagus had greater (P < 0.05) wall tension and were less (P < 0.05) deformable
than the mid- or distal esophagus. Sensory thresholds were lower (P < 0.05) in the
proximal compared with the mid- or distal esophagus. Biomechanical and sensory
parameters are not uniform along the length of the esophagus. The striated muscle
portion is more sensitive and less compliant than the smooth muscle portion.
These differences could affect the results of balloon distension tests of the
esophagus.
133. Patel, R. S.; Rao, S. S. Biomechanical and sensory parameters of the human esophagus
at four levels. Am-J-Physiol. 1998 Aug; 275(2 Pt 1): G187-91; ISSN: 0002-9513.
UNITED-STATES. The biomechanical and sensory characteristics of the lower
esophageal sphincter (LES) and those of the striated and smooth muscle portions
of the esophagus have not been compared in humans. Our aim was to determine
sensory perception, cross-sectional area (CSA), and biomechanical parameters at
different levels of the esophagus. We studied 11 healthy volunteers, using
impedance planimetry. Intermittent balloon distensions (5-60 cmH2O) were
performed at four sites: 1) the LES, 2) 5 cm above LES (distal), 3) 10 cm above
LES (mid), and 4) 5 cm below the upper esophageal sphincter (proximal). During
these distensions, CSAs, biomechanical parameters, and sensory responses were
measured. The mid-esophagus had a higher (P < 0.05) CSA than the distal
esophagus. The LES had the smallest CSA (P < 0.05). The LES and the proximal
esophagus had greater (P < 0.05) wall tension and were less (P < 0.05) deformable
than the mid- or distal esophagus. Sensory thresholds were lower (P < 0.05) in the
proximal compared with the mid- or distal esophagus. Biomechanical and sensory
parameters are not uniform along the length of the esophagus. The striated muscle
portion is more sensitive and less compliant than the smooth muscle portion.
These differences could affect the results of balloon distension tests of the
esophagus.
134. Pavon, N.; Vidal, L.; Alvarez, P.; Blanco, L.; Torres, A.; Rodriguez, A.; Macias, R.
[Behavioral evaluation of the unilateral lesion model in rats using 6-
hydroxydopamine. Correlation between the rotations induced by D-amphetamine,
apomorphine and the manual dexterity test]. Evaluacion conductual del modelo de
lesion unilateral en ratas con 6-hidroxidopamina. Correlacion entre las rotaciones
inducidas por D-anfetamina, apomorfina y la prueba de habilidades manuales.
Rev-Neurol. 1998 Jun; 26(154): 915-8; ISSN: 0210-0010.
SPAIN. INTRODUCTION: Evaluation of rotatory activity induced by
dopaminergic agonists is the most widely used test of conduct for the
measurement of dopaminergic depletion of a unilateral lesion of the striatonigral
pathway caused by 6-hydroxydopamine (6-OHDA) in rats, since it is
quantitatively related to the extension of the dopaminergic denervation.
OBJECTIVE: The objective of this study was to evaluate, from different angles,
the changes in conduct seen in the model of unilateral lesion with 6-OHDA and to
establish correlation with the rotation induced by D-amphetamine and by
apomorphine and the ladder test. MATERIAL AND METHODS: Male Wistar
rats were used. Lesions were produced in the SNpc by stereotactic injection of 6-
OHDA into the right hemisphere and the effectiveness of the lesions was studied
using the rotary conduct induced by D-amphetamine and apomorphine. The
motor ability of the front legs was measured by the ladder test, carried out under
standard and forced conditions. RESULTS: All the animals with lesions had
difficulty in reaching food with both legs, although the most pronounced deficit
was in the leg contralateral to the lesion. The ladder test correlated better with
rotatory activity induced by apomorphine than by D-amphetamine.
CONCLUSION: The animals with most dopamine loss showed most deficient
use of their front legs.. 0; 1199-18-4; 51-61-6; 51-64-9; 58-00-4.
135. Rada, P.; Mark, G. P.; Hoebel, B. G. Galanin in the hypothalamus raises dopamine
and lowers acetylcholine release in the nucleus accumbens: a possible mechanism
for hypothalamic initiation of feeding behavior. Brain-Res. 1998 Jul 6; 798(1-2):
1-6; ISSN: 0006-8993.
NETHERLANDS. Rats were prepared with two implanted guide shafts, one for
microdialysis to measure extracellular dopamine (DA) and acetylcholine (ACh) in
the posterior, medial nucleus accumbens (NAc), and the other for microinjection
of galanin, neuropeptide Y or saline in the hypothalamic paraventricular nucleus
(PVN). There was an increase in DA release and a decrease in ACh in the NAc
following microinjections of galanin into the PVN. The effect was observed only
in rats for which identical galanin injections induced feeding in separate tests.
Ringer injections had no effects. Unlike galanin, neuropeptide Y in the PVN
induced eating without altering DA/ACh; whereas earlier results showed that
norepinephrine in the PVN works like galanin. These results suggest that galanin
initiates feeding, in part, by activating the mesolimbic DA system and
suppressing intrinsic cholinergic activity in the NAc. This may prime
instrumental behavior with DA while disinhibiting behavior by lowering ACh.
Copyright 1998 Elsevier Science B.V. All rights reserved.. 0; 51-61-6; 51-84-3;
88813-36-9.
136. Ramachandran, V. S.; Hirstein, W. The perception of phantom limbs. The D. O. Hebb
lecture. Brain. 1998 Sep; 121( Pt 9): 1603-30; ISSN: 0006-8950.
ENGLAND. Almost everyone who has a limb amputated will experience a
phantom limb--the vivid impression that the limb is not only still present, but in
some cases, painful. There is now a wealth of empirical evidence demonstrating
changes in cortical topography in primates following deafferentation or
amputation, and this review will attempt to relate these in a systematic way to
the clinical phenomenology of phantom limbs. With the advent of non-invasive
imaging techniques such as MEG (magnetoencephalogram) and functional MRI,
topographical reorganization can also be demonstrated in humans, so that it is
now possible to track perceptual changes and changes in cortical topography in
individual patients. We suggest, therefore, that these patients provide a valuable
opportunity not only for exploring neural plasticity in the adult human brain but
also for understanding the relationship between the activity of sensory neurons
and conscious experience. We conclude with a theory of phantom limbs, some
striking demonstrations of phantoms induced in normal subjects, and some
remarks about the relevance of these phenomena to the question of how the brain
constructs a 'body image.'.
137. Ramachandran, V. S.; Hirstein, W. The perception of phantom limbs. The D. O. Hebb
lecture. Brain. 1998 Sep; 121( Pt 9): 1603-30; ISSN: 0006-8950.
ENGLAND. Almost everyone who has a limb amputated will experience a
phantom limb--the vivid impression that the limb is not only still present, but in
some cases, painful. There is now a wealth of empirical evidence demonstrating
changes in cortical topography in primates following deafferentation or
amputation, and this review will attempt to relate these in a systematic way to
the clinical phenomenology of phantom limbs. With the advent of non-invasive
imaging techniques such as MEG (magnetoencephalogram) and functional MRI,
topographical reorganization can also be demonstrated in humans, so that it is
now possible to track perceptual changes and changes in cortical topography in
individual patients. We suggest, therefore, that these patients provide a valuable
opportunity not only for exploring neural plasticity in the adult human brain but
also for understanding the relationship between the activity of sensory neurons
and conscious experience. We conclude with a theory of phantom limbs, some
striking demonstrations of phantoms induced in normal subjects, and some
remarks about the relevance of these phenomena to the question of how the brain
constructs a 'body image.'.
138. Rao, S. S. The technical aspects of biofeedback therapy for defecation disorders.
Gastroenterologist. 1998 Jun; 6(2): 96-103; ISSN: 1065-2477.
UNITED-STATES. Neuromuscular conditioning using biofeedback techniques is
a useful method of treatment for patients with refractory defecation disorders
such as fecal incontinence or constipation with obstructive defecation. This article
provides current perspectives regarding the principles and techniques of
performing biofeedback therapy. In patients with incontinence, the goals are to
improve the strength of the anal sphincter, improve sensory perception, and
improve coordination between the rectum and anal sphincter. In patients with
obstructive defecation, the goals are to relax the anal sphincter, improve rectoanal
coordination, and improve sensory perception. Neuromuscular conditioning is an
instrument-based learning technique. Over the years, several devices and methods
have become available for performing this training, but no single method is either
superior or universally popular. The three modalities that are commonly used for
neuromuscular conditioning are visual, verbal, and audio feedback. Ideally, the
training program should be customized for each patient based on the underlying
dysfunction(s). After biofeedback therapy, symptomatic improvement has been
reported in 70 to 80% of patients with either incontinence or obstructive
defecation. Recent studies also demonstrated objective improvement in anorectal
function. In the future, it is likely that simpler and user-friendly, solid-state
computerized systems may facilitate a wider use of this treatment.
139. Rao, S. S. The technical aspects of biofeedback therapy for defecation disorders.
Gastroenterologist. 1998 Jun; 6(2): 96-103; ISSN: 1065-2477.
UNITED-STATES. Neuromuscular conditioning using biofeedback techniques is
a useful method of treatment for patients with refractory defecation disorders
such as fecal incontinence or constipation with obstructive defecation. This article
provides current perspectives regarding the principles and techniques of
performing biofeedback therapy. In patients with incontinence, the goals are to
improve the strength of the anal sphincter, improve sensory perception, and
improve coordination between the rectum and anal sphincter. In patients with
obstructive defecation, the goals are to relax the anal sphincter, improve rectoanal
coordination, and improve sensory perception. Neuromuscular conditioning is an
instrument-based learning technique. Over the years, several devices and methods
have become available for performing this training, but no single method is either
superior or universally popular. The three modalities that are commonly used for
neuromuscular conditioning are visual, verbal, and audio feedback. Ideally, the
training program should be customized for each patient based on the underlying
dysfunction(s). After biofeedback therapy, symptomatic improvement has been
reported in 70 to 80% of patients with either incontinence or obstructive
defecation. Recent studies also demonstrated objective improvement in anorectal
function. In the future, it is likely that simpler and user-friendly, solid-state
computerized systems may facilitate a wider use of this treatment.
140. Rauhala, P.; Khaldi, A.; Mohanakumar, K. P.; Chiueh, C. C. Apparent role of
hydroxyl radicals in oxidative brain injury induced by sodium nitroprusside. Free-
Radic-Biol-Med. 1998 May; 24(7-8): 1065-73; ISSN: 0891-5849.
UNITED-STATES. Sodium nitroprusside (disodium nitroferricyanide) has been
suggested to cause cytotoxicity through either the release of cyanide and/or nitric
oxide. The present study investigated a possible mechanism that after a brief
release of nitric oxide, iron moiety of breakdown products of sodium
nitroprusside could cause a long lasting oxidative stress, such as hydroxyl radical
generation, lipid peroxidation and cytotoxicity. Intranigral administration of
sodium nitroprusside (0-16.8 nmol) to rats induced an acute increase in lipid
peroxidation in the substantia nigra and a chronic dopamine depletion in the
caudate nucleus. Photodegraded (nitric oxide-exhausted) sodium nitroprusside,
however, still produced lipid peroxidation and neurotoxicity in the midbrain.
Moreover, non-iron containing nitric oxide-donor compounds, such as S-nitroso-
N-acetylpenicillamine, did not cause oxidative brain injury in vivo suggesting that
nitric oxide may not mediate neurotoxicity induced by sodium nitroprusside.
Additional in vitro studies demonstrated that both freshly prepared (nitric oxide
donor) and photodegraded (nitric oxide-exhausted) sodium nitroprusside generated
hydroxyl radicals in the presence of ascorbate and also increased lipid
peroxidation in brain homogenates. These pro-oxidative effects of sodium
nitroprusside were blocked by nitric oxide, S-nitroso-N-acetylpenicillamine,
oxyhemoglobin, and deferoxamine (iron chelator). The present results suggest that
iron moiety, rather than nitric oxide, may mediate the pro-oxidative properties of
sodium nitroprusside. With this new information in mind, the misuse of sodium
nitroprusside as a selective nitric oxide donor in both basic and clinical uses should
be urgently addressed.. 0; 0; 10102-43-9; 15078-28-1; 3352-57-6; 50-81-7; 52-
67-5; 70-51-9; 7439-89-6; 7722-84-1.
141. Robertson, I. H.; Mattingley, J. B.; Rorden, C.; Driver, J. Phasic alerting of neglect
patients overcomes their spatial deficit in visual awareness. Nature. 1998 Sep 10;
395(6698): 169-72; ISSN: 0028-0836.
ENGLAND. Patients with extensive damage to the right hemisphere of their
brain often exhibit unilateral neglect of the left side of space. The spatial attention
of these patients is strongly biased towards the right, so their awareness of visual
events on the left is impaired. Extensive right-hemisphere lesions also impair tonic
alertness (the ability to maintain arousal). This nonspatial deficit in alertness is
often considered to be a different problem from spatial neglect, but the two
impairments may be linked. If so, then phasically increasing the patients' alertness
should temporarily ameliorate their spatial bias in awareness. Here we provide
evidence to support this theory. Right-hemisphere-neglect patients judged
whether a visual event on the left preceded or followed a comparable event on the
right. They became aware of left events half a second later than right events on
average. This spatial imbalance in the time course of visual awareness was
corrected when a warning sound alerted the patients phasically. Even a warning
sound on the right accelerated the perception of left visual events in this way.
Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual
awareness after brain injury.
142. Robertson, I. H.; Mattingley, J. B.; Rorden, C.; Driver, J. Phasic alerting of neglect
patients overcomes their spatial deficit in visual awareness. Nature. 1998 Sep 10;
395(6698): 169-72; ISSN: 0028-0836.
ENGLAND. Patients with extensive damage to the right hemisphere of their
brain often exhibit unilateral neglect of the left side of space. The spatial attention
of these patients is strongly biased towards the right, so their awareness of visual
events on the left is impaired. Extensive right-hemisphere lesions also impair tonic
alertness (the ability to maintain arousal). This nonspatial deficit in alertness is
often considered to be a different problem from spatial neglect, but the two
impairments may be linked. If so, then phasically increasing the patients' alertness
should temporarily ameliorate their spatial bias in awareness. Here we provide
evidence to support this theory. Right-hemisphere-neglect patients judged
whether a visual event on the left preceded or followed a comparable event on the
right. They became aware of left events half a second later than right events on
average. This spatial imbalance in the time course of visual awareness was
corrected when a warning sound alerted the patients phasically. Even a warning
sound on the right accelerated the perception of left visual events in this way.
Nonspatial phasic alerting can thus overcome disabling spatial biases in perceptual
awareness after brain injury.
143. Rodriguez, M. C.; Obeso, J. A.; Olanow, C. W. Subthalamic nucleus-mediated
excitotoxicity in Parkinson's disease: a target for neuroprotection. Ann-Neurol.
1998 Sep; 44(3 Suppl 1): S175-88; ISSN: 0364-5134.
UNITED-STATES. Dopamine deficiency causes disinhibition and overactivity
of the subthalamic nucleus (STN). Output neurons from the STN are excitatory
and use glutamate as a neurotransmitter. They project to the external and internal
segments of the globus pallidum (GPe and GPi), the substantia nigra pars
reticulata (SNr), and the pedunculopontine nucleus (PPN). In addition, STN
neurons provide excitatory innervation to dopaminergic (DA) neurons in the
substantia nigra pars compacta (SNc) that contain glutamate receptors.
Stimulation of the STN induces bursting activity in SNc dopaminergic neurons.
This raises the possibility that the disinhibition of STN neurons that occurs as a
result of a dopamine lesion might induce excitotoxic damage in target structures,
including the SNc. In addition, the reduction in complex I activity found in the
nigra in Parkinson's disease (PD) may cause mitochondrial dysfunction and make
SNc dopaminergic neurons vulnerable to even physiologic concentrations of
glutamate. We postulate that the dopamine loss that occurs in PD produces
augmented STN activity which, in turn, causes further damage to vulnerable
dopaminergic neurons, thereby creating a scenario for an increasing cycle of
neuronal loss in the SNc. In addition, STN overactivity could, in theory, cause
damage to the GPi, SNr, and PPN and thereby account for the development of
parkinsonian features that do not respond to levodopa in patients with advanced
disease. This hypothesis suggests that pharmacologic or surgical therapies that
reduce STN neuronal overactivity or block glutamate receptors in the SNc and
other target structures might be neuroprotective and might slow or halt the
progression of neurodegeneration in PD.. 0; 0.
144. Rossing, M. A. Genetic influences on smoking: candidate genes. Environ-Health-
Perspect. 1998 May; 106(5): 231-8; ISSN: 0091-6765.
UNITED-STATES. Twin studies consistently indicate important genetic
influences on multiple aspects of smoking behavior, including both initiation and
cessation; however, knowledge regarding the role of specific genes is extremely
limited. Habit-forming actions of nicotine appear to be triggered primarily at
nicotinic receptors on the cell bodies of dopaminergic neurons in the mesolimbic
"reward" system of the brain, a region implicated in addiction to other substances
including cocaine, opiates, and alcohol. Important aspects of the dopaminergic
pathway include synthesis of dopamine in dopaminergic neurons, release of
dopamine by presynaptic neurons, receptor activation of postsynaptic neurons,
dopamine re-uptake by presynaptic neurons, and metabolism of released
dopamine. Research examining the role of allelic variation in genes involved in
these functions is being actively pursued with respect to addictive behavior as
well as personality traits and psycho- and neuropathologic conditions and has
implications for smoking research. In addition, genetic differences in nicotinic
receptors or nicotine metabolism might reasonably be hypothesized to play a role
in smoking addiction. A role of dopaminergic or other genes in smoking cessation
is of particular potential importance, as research in this area may lead to the
identification of subgroups of individuals for whom pharmacologic cessation aids
may be most effective.. 0; 51-61-6; 54-11-5.
145. Schilstrom, B.; Svensson, H. M.; Svensson, T. H.; Nomikos, G. G. Nicotine and food
induced dopamine release in the nucleus accumbens of the rat: putative role of
alpha7 nicotinic receptors in the ventral tegmental area. Neuroscience. 1998 Aug;
85(4): 1005-9; ISSN: 0306-4522.
UNITED-STATES. We have recently shown that the stimulatory effect of
nicotine on dopamine output in the nucleus accumbens is largely dependent upon
an enhanced glutamate transmission via N-methyl-D-aspartate receptors, possibly
through stimulation of nicotinic receptors localized presynaptically on
glutamatergic afferents in the ventral tegmental area. Given that nicotinic alpha7
receptors have been proposed to be involved in presynaptic regulation of
glutamate release, we investigated whether alpha7 receptors underlie such a
mechanism in the ventral tegmental area. For this purpose, by utilizing
microdialysis we measured dopamine release in the nucleus accumbens in
response to systemic nicotine, with, or without, concomitant infusion into the
ventral tegmental area of the selective alpha7 receptor antagonist
methyllycaconitine. To test also whether alpha7 nicotinic receptor antagonism
within the ventral tegmental area affected a natural reward-mediated increase in
dopamine release in the nucleus accumbens, we employed a model of schedule-
induced feeding. Intrategmental administration of methyllycaconitine decreased
both the nicotine-induced and the food-induced dopamine release in the nucleus
accumbens. We suggest that alpha7 nicotinic receptors in the ventral tegmental
area are involved in the acute effect of nicotine on dopamine release in the nucleus
accumbens and conclude that the mechanism, by which nicotine stimulates the
mesolimbic dopaminergic system, may be an essential constituent of the natural
reward-related circuits in brain.. 0; 0; 0; 21019-30-7; 302-27-2; 51-61-6; 54-11-5.
146. Schipper, H. M.; Vininsky, R.; Brull, R.; Small, L.; Brawer, J. R. Astrocyte
mitochondria: a substrate for iron deposition in the aging rat substantia nigra. Exp-
Neurol. 1998 Aug; 152(2): 188-96; ISSN: 0014-4886.
UNITED-STATES. Little is currently known concerning the cellular substrates
for, and the mechanisms mediating the pathological deposition of, redox-active
brain iron in Parkinson's disease. In various subcortical brain regions, populations
of astroglia progressively accumulate peroxidase-positive cytoplasmic inclusions
derived from effete, iron-laden mitochondria. In the present study, histochemical,
ultrastructural, and elemental microanalytical techniques were used to demonstrate
the existence of peroxidase-positive astroglia in the substantia nigra of adult rats.
At 4 months of age and earlier, few GFAP-positive nigral astroglia contained
small, electron-dense cytoplasmic inclusions which exhibited faint endogenous
peroxidase activity (diaminobenzidine reaction product) and no detectable iron by
microprobe analysis. In contrast, by 14-18 months of age, there was a significant,
fourfold increase in numbers of peroxidase-positive astrocyte inclusions in the
substantia nigra. The nigral gliosomes in the older animals were heterogeneously
electron dense, immunoreactive for ubiquitin and a mitochondrial epitope, and
often exhibited X-ray emission peaks for iron. Copper peaks were also detected in
a minority of nigral gliosomes. Previous in vitro work indicated that the iron-
mediated peroxidase activity in these cells promotes the bioactivation of
dopamine and other catechols to neurotoxic free radical intermediates. Thus,
mitochondrial sequestration of redox-active iron in aging nigral astroglia may be
one factor predisposing the senescent nervous system to parkinsonism and other
neurodegenerative disorders. Copyright 1998 Academic Press.. 0; 7439-89-6.
147. Semba, J.; Wakuta, M. S. Regional differences in the effects of glutamate uptake
inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid on extracellular amino acids and
dopamine in rat brain: an in vivo microdialysis study. Gen-Pharmacol. 1998 Sep;
31(3): 399-404; ISSN: 0306-3623.
ENGLAND. The effects of the glutamate transporter inhibitor, trans-PDC, on
extracellular amino acids, were investigated in the frontal cortex, striatum,
hippocampus and cerebellum of rats using in vivo microdialysis. Trans-PDC
infusion (0.1, 1, 10 mM) dose-dependently increased Glu and Asp levels, and
these increases in the cerebellum were smaller than those in other brain regions. A
small but significant dose-dependent increase was observed for Gly and Tau.
However, high extracellular Glu induced by trans-PDC was not sufficient to
increase extracellular DA in the striatum and frontal cortex.. 0; 0; 0; 0; 0; 51-61-6;
56-86-0; 70025-48-8; 99319-03-6.
148. Sidyakin, V. G.; Pavlenko, V. B.; Kulichenko, A. M.; Gorelova, E. V.; Pavlenko, O.
M. Activity of substantia nigra neurons in the cat brain during a self-initiated
behavioral act. Neurosci-Behav-Physiol. 1998 May; 28(3): 238-43; ISSN: 0097-
0549.
UNITED-STATES. Cats were trained to perform a self-initiated behavioral act in
the form of an operant food-obtaining reflex with defined time requirements.
Activity was recorded from 50 dopaminergic neurons (identified in terms of their
low frequency of background activity and long action potentials) and 67
nondopaminergic neurons of the substantia nigra and adjacent region.
Dopaminergic neurons were the more responsive. Prior to EMG activation, the
activity of 33 (66%) of these cells changed, and 44 (88%) showed changes in
activity on movement. Dopaminergic neurons showed increased activity during
the period of waiting for the conditioned stimulus, predicting the release of
reinforcement or its absence. These cells were more frequently activated in
response to a positive signal and reinforcement and were more frequently
inhibited in the absence of reinforcement. The high reactivity of dopaminergic
neurons during execution of a movement task could be explained by the
involvement of a cognitive component, i.e., determining the point at which the
movement should start.. 51-61-6.
149. Sills, T. L.; Onalaja, A. O.; Crawley, J. N. Mesolimbic dopaminergic mechanisms
underlying individual differences in sugar consumption and amphetamine
hyperlocomotion in Wistar rats. Eur-J-Neurosci. 1998 May; 10(5): 1895-902;
ISSN: 0953-816X.
FRANCE. Individual differences within strains of rats have been demonstrated
for dopamine-mediated behaviours and responses to dopaminergic drugs.
Differences in mesolimbic dopamine function may underlie individual differences
in some of these behaviours, including sugar consumption and amphetamine
hyperlocomotion. The present study addressed two potential mechanisms for
these differences in dopamine-mediated behaviours. The possibility of functional
differences in dopamine receptor subtypes was tested in LOW and HIGH sugar
feeders. LOW and HIGH feeders did not differ in their response to the partial D1
agonist SKF-38393. The highest dose (2.5 mg/kg) of the D2 agonist quinpirole
stimulated locomotor activity to a greater degree in a subset of HIGH sugar
feeders as compared with LOW feeders. All doses of amphetamine induced a
greater locomotor response in HIGH feeders as compared with LOW feeders, and
HIGH feeders exhibited higher levels of extracellular dopamine in the nucleus
accumbens than LOW feeders following exposure to sugar and treatment with
amphetamine. These results support the interpretation that LOW and HIGH
feeders exhibit differences in presynaptic nucleus accumbens dopamine function
that account for the expression of individual differences in sugar consumption and
response to amphetamine treatments. A subset of HIGH feeders may also exhibit
greater D2 receptor function.. 0; 0; 0; 0; 300-62-9; 51-61-6; 67287-49-4; 85760-
74-3.
150. Simpson, W. A.; Newman, A. Motion detection and directional tuning. Vision-Res.
1998 Jun; 38(11): 1593-604; ISSN: 0042-6989.
ENGLAND. A random dot pattern was presented which made two jumps in
various directions with a variable delay between them. The jumps occurred at the
frame transitions of a 3-frame apparent motion sequence. The variation in
detectability with the directional difference and the temporal separation of the
jumps allows us to make inferences about directional tuning and the temporal
response of the motion detection mechanism. The detectability of a pair of jumps
was highest when the delay between the jumps was short and the difference in the
jump directions was small. In all cases the data were well fitted with a vector
version of the speed energy model earlier proposed by Simpson. The model
supposes that the two input vectors are temporally filtered, squared and
integrated. Using the model, the autocorrelation function of the motion system's
temporal impulse response can be found. This function shows the filter to be
lowpass. According to the model, the shape of the threshold or d' locus as a
function of the difference in the directions of the two jumps does not show the
tuning of a motion mechanism. A tuned mechanism will respond well to a jump in
its preferred direction, but less well to any other jump. Instead we show that the
apparent tuning evident in the threshold and d' loci is due to the way in which the
two jump vectors, each fully recovered, are combined in a vector sum.
151. Simpson, W. A.; Newman, A. Motion detection and directional tuning. Vision-Res.
1998 Jun; 38(11): 1593-604; ISSN: 0042-6989.
ENGLAND. A random dot pattern was presented which made two jumps in
various directions with a variable delay between them. The jumps occurred at the
frame transitions of a 3-frame apparent motion sequence. The variation in
detectability with the directional difference and the temporal separation of the
jumps allows us to make inferences about directional tuning and the temporal
response of the motion detection mechanism. The detectability of a pair of jumps
was highest when the delay between the jumps was short and the difference in the
jump directions was small. In all cases the data were well fitted with a vector
version of the speed energy model earlier proposed by Simpson. The model
supposes that the two input vectors are temporally filtered, squared and
integrated. Using the model, the autocorrelation function of the motion system's
temporal impulse response can be found. This function shows the filter to be
lowpass. According to the model, the shape of the threshold or d' locus as a
function of the difference in the directions of the two jumps does not show the
tuning of a motion mechanism. A tuned mechanism will respond well to a jump in
its preferred direction, but less well to any other jump. Instead we show that the
apparent tuning evident in the threshold and d' loci is due to the way in which the
two jump vectors, each fully recovered, are combined in a vector sum.
152. Sullivan, A. M.; Opacka Juffry, J.; Blunt, S. B. Long-term protection of the rat
nigrostriatal dopaminergic system by glial cell line-derived neurotrophic factor
against 6-hydroxydopamine in vivo. Eur-J-Neurosci. 1998 Jan; 10(1): 57-63;
ISSN: 0953-816X.
FRANCE. Glial cell-line-derived neurotrophic factor (GDNF) has been shown to
enhance the survival of dopaminergic neurones both in vitro and in vivo, and to
protect the rodent dopaminergic system from neurotoxic damage. However, most
previous studies have only examined the short-term protective effects of GDNF.
We have investigated the long-term effects of GDNF on a 6-hydroxydopamine (6-
OHDA)-induced lesion of the rat medial forebrain bundle (MFB), which results in
complete and irreversible destruction of the nigrostriatal pathway, and is a robust
model of Parkinson's disease. GDNF was administered ipsilaterally above the
substantia nigra and into the lateral ventricle immediately before a unilateral 6-
OHDA injection into the MFB. The effects of GDNF were examined in vivo by
behavioural testing and positron emission tomography (PET) at weekly intervals,
for 12 weeks. GDNF prevented the development of amphetamine-induced
rotations at all time-points. PET studies, using [11C]-RTI-121 as a tracer for the
dopamine transporter, indicated that GDNF prevented 6-OHDA-induced
reduction of dopamine reuptake sites in the ipsilateral striatum. Post-mortem
neurochemical analysis at 13 weeks after surgery found that GDNF significantly
inhibited 6-OHDA-induced loss of dopamine, 3,4-dihydroxyphenylacetic acid and
homovanillic acid in the ipsilateral striatum. Immunocytochemistry showed that
GDNF reduced 6-OHDA-induced loss of tyrosine hydroxylase-positive neurones
in both the substantia nigra pars compacta and ventral tegmental area. We have
shown that a single treatment with GDNF can confer long-term protective effects
against a 6-OHDA lesion, which suggests that this factor may be useful for the
treatment of Parkinson's disease.. EC 1.14.16.2; 0; 0; 0; 0; 102-32-9; 1199-18-4;
306-08-1; 51-61-6.
153. Suzuki, M.; Sun, Y. J.; Murata, M.; Kurachi, M. Widespread expression of Fos
protein induced by acute haloperidol administration in the rat brain. Psychiatry-
Clin-Neurosci. 1998 Jun; 52(3): 353-9; ISSN: 1323-1316.
AUSTRALIA. The effect of acute haloperidol administration on Fos protein
expression was examined immunohistochemically in discrete regions of the rat
brain. Male Wistar rats were injected subcutaneously (s.c.) with 0.1, 0.25, or 1.0
mg/kg of haloperidol. Two h after the injection, the rats were perfused, and the
numbers of Fos immunoreactive neurons were counted in 24 brain regions. In
contrast to the limited changes in Fos immunoreactivity at the low dose of
haloperidol (0.1 mg/kg), the moderate dose (0.25 mg/kg) induced widespread
increases in Fos-positive neurons in the rat brain. Large increases were produced
in the caudate-putamen, nucleus accumbens, central amygdaloid nucleus,
dorsomedial hypothalamic nucleus, hippocampus CA1 and substantia nigra pars
compacta. Moderate increases were observed in the entorhinal cortex, lateral
septum, lateral habenula, lateral amygdaloid nucleus, dentate gyrus, and
mesencephalic central grey. Mild increases were induced in the anterior cingulate,
temporal, occipital and perirhinal cortex, and central medial thalamic nucleus. The
distribution of changes in Fos immunoreactivity at the high dose of haloperidol
(1.0 mg/kg) were comparable to their distribution at the moderate dose. These
findings indicate that the effect of acute haloperidol on Fos expression is widely
distributed in the rat brain beyond the previously known dopamine-rich areas at
the dose which produces plasma levels equivalent to those within the therapeutic
range used clinically in humans. Further studies on the effects of chronic
antipsychotic treatment are needed in order to identify the sites of the therapeutic
action of antipsychotic drugs.. 0; 0; 52-86-8.
154. Suzuki, Y.; Awaya, S.; Uno, S. Motion perception tested with reversing grating in
Duane's syndrome. Jpn-J-Ophthalmol. 1998 May; 42(3): 199-203; ISSN: 0021-
5155.
JAPAN. Many papers have reported that motion perception asymmetry (MPA)
is replaced by motion perception symmetry (MPS) by the 4th to 5th month after
birth, when stereopsis starts to occur in normal infants. Duane's syndrome is a
congenital motor abnormality, it does, however, reportedly show good stereopsis.
We confirmed the stereopsis in Duane's syndrome and checked the motion
perception (MP) by using the Reversing Grating Test to investigate if the
congenital motor abnormality affects the MP in patients whose binocular sensory
system is well developed. Thirty-eight Duane's syndrome patients aged 3 to 45
years were included in the present study. They were divided into 24 cases of
Duane I, 9 cases of Duane II, 5 cases of Duane III. The Titmus Stereo Tests, Lang
Stereotest, and TV-Random Dot Stereo Test were used to examine the stereopsis.
Thirty-four patients had good stereopsis, and 4 had poor stereopsis. None of
them showed MPA in any spatial frequencies (1/ 4, 1/2, 1 cycles/degree)
examined. The Reversing Grating Test is useful for examining MPA in strabismus
patients with eye movement limitations.
155. Suzuki, Y.; Awaya, S.; Uno, S. Motion perception tested with reversing grating in
Duane's syndrome. Jpn-J-Ophthalmol. 1998 May; 42(3): 199-203; ISSN: 0021-
5155.
JAPAN. Many papers have reported that motion perception asymmetry (MPA)
is replaced by motion perception symmetry (MPS) by the 4th to 5th month after
birth, when stereopsis starts to occur in normal infants. Duane's syndrome is a
congenital motor abnormality, it does, however, reportedly show good stereopsis.
We confirmed the stereopsis in Duane's syndrome and checked the motion
perception (MP) by using the Reversing Grating Test to investigate if the
congenital motor abnormality affects the MP in patients whose binocular sensory
system is well developed. Thirty-eight Duane's syndrome patients aged 3 to 45
years were included in the present study. They were divided into 24 cases of
Duane I, 9 cases of Duane II, 5 cases of Duane III. The Titmus Stereo Tests, Lang
Stereotest, and TV-Random Dot Stereo Test were used to examine the stereopsis.
Thirty-four patients had good stereopsis, and 4 had poor stereopsis. None of
them showed MPA in any spatial frequencies (1/ 4, 1/2, 1 cycles/degree)
examined. The Reversing Grating Test is useful for examining MPA in strabismus
patients with eye movement limitations.
156. Sziraki, I.; Mohanakumar, K. P.; Rauhala, P.; Kim, H. G.; Yeh, K. J.; Chiueh, C. C.
Manganese: a transition metal protects nigrostriatal neurons from oxidative stress
in the iron-induced animal model of parkinsonism. Neuroscience. 1998 Aug; 85(4):
1101-11; ISSN: 0306-4522.
UNITED-STATES. It has been suggested that transition metals such as iron and
manganese produce oxidative injury to the dopaminergic nigrostriatal system.
which may play a critical role in the pathogenesis of Parkinson's disease.
Intranigral infusion of ferrous citrate (0 to 8.4 nmol, i.n.) acutely increased lipid
peroxidation in the substantia nigra and dopamine turnover in the caudate nucleus.
Subsequently, it caused a severe depletion of dopamine levels in the rat caudate
nucleus. In contrast to iron's pro-oxidant effect, manganese (up to 30 nmol, i.n.)
causes neither lipid peroxidation nor nigral injury/dopamine depletion. Manganese
(1.05 to 4.2 nmol, i.n.) dose-dependently protected nigral neurons from iron-
induced oxidative injury and dopamine depletion. Manganese also suppressed
acute increase in dopamine turnover and contralateral turning behaviour induced
by iron. In brain homogenates manganese (0 to 10 microM) concentration-
dependently inhibited propagation of lipid peroxidation caused by iron (0 to 5
microM). Without the contribution of manganese-superoxide dismutase
manganese was still effective in sodium azide and/or heat-pretreated brain
homogenates. Surprisingly, iron but not manganese, catalysed the Fenton reaction
or the conversion of hydrogen peroxide to hydroxyl radicals. The results indicate
that iron and manganese are two transition metals mediating opposite effects in
the nigrostriatal system, as pro-oxidant and antioxidant, respectively. In
conclusion, intranigral infusion of iron, but not manganese, provides an animal
model for studying the pathophysiological role of oxidant and oxidative stress in
nigrostriatal degeneration and Parkinsonism. The present results further suggest
that the atypical antioxidative properties of manganese may protect substantia
nigra compacta neurons from iron-induced oxidative stress.. EC 1.15.1.1; 0; 3352-
57-6; 51-61-6; 7439-89-6; 7439-96-5.
157. Tanda, G.; Di Chiara, G. A dopamine-mu1 opioid link in the rat ventral tegmentum
shared by palatable food (Fonzies) and non-psychostimulant drugs of abuse. Eur-
J-Neurosci. 1998 Mar; 10(3): 1179-87; ISSN: 0953-816X.
FRANCE. The role of mu1 opioid receptors in the stimulation of dopamine
transmission in the rat nucleus accumbens by an unusual palatable food (Fonzies)
and non-psychostimulant drugs of abuse was investigated by the use of
naloxonazine, a pseudo-irreversible antagonist of mu1 opioid receptors. Feeding of
Fonzies stimulated dopamine release in the medial prefrontal cortex and in the
shell, but not in the core of the nucleus accumbens. Pretreatment with
naloxonazine given systemically (15 mg/kg i.p. 20 h before) completely prevented
the stimulation of dopamine release in the shell of the nucleus accumbens by
Fonzies without affecting that in the prefrontal cortex. Systemic pretreatment
with naloxonazine reduced or, depending on the dose, abolished, the stimulation of
dopamine release in the nucleus accumbens shell by morphine, nicotine and
ethanol, but did not affect that by haloperidol. Naloxonazine also prevented the
stimulatory effects of Fonzies, nicotine and morphine on nucleus accumbens
dopamine transmission when infused bilaterally in the ventral tegmental area. The
results indicate that mu1 opioid receptors in the ventral tegmentum play a major
role in the stimulant effects of food and drugs of abuse on mesolimbic dopamine
transmission.. 0; 0; 0; 0; 465-65-6; 51-61-6; 54-11-5; 57-27-2; 82824-01-9.
158. Turle, N.; Saget, A.; Zouani, B.; Risso, J. J. Neurochemical studies of narcosis: a
comparison between the effects of nitrous oxide and hyperbaric nitrogen on the
dopaminergic nigro-striatal pathway. Neurochem-Res. 1998 Jul; 23(7): 997-1003;
ISSN: 0364-3190.
UNITED-STATES. Inert gas narcosis is a neurological syndrome inducing several
psychomotor disorders. Nitrogen narcosis represents the major cause of
performances decrease concerning divers, in the depth range of 30 to 90 meters
(0.3 to 0.9 MegaPascal). As narcosis affects motor functions, we chose to study
the nigro-striatal dopaminergic pathway owing to its involvement in psychomotor
disorders. The aim of this study is to compare, in the Sprague-Dawley rats
striatium, changes in extracellular concentrations of Dopamine and its metabolites:
Dihydroxyphenylacetic Acid (DOPAC) and Homovanillic Acid (HVA) under a
normobaric narcosis (20; 40, and 60% of Nitrous Oxide (N2O)) on one hand, and
under 0.9 MegaPascal of Nitrox (Nitrogen Oxygen normoxic mixture) on the other
hand. In fact, if these two conditions are similar, normobaric narcosis would allow
us to explain nitrogen narcosis mechanisms without any pressure effect. The first
emergence of Dopamine and metabolites variations occurs around 40% of N2O.
Dopamine decreases by 45% and is accompanied by a DOPAC diminution of 7%
while HVA concentrations remain constant. Under 60% N2O, these decrease have
a greater amplitude. The Dopamine variations obtained under 0.9 Mpa of Nitrox
are closed to alterations induced by 60% of N2O (DA decreases by 70%)..
10024-97-2; 102-32-9; 306-08-1; 51-61-6; 7727-37-9.
159. van, den Buuse M.; Wilks, D. P.; Cornish, J. L. Inhibition of cardiac baroreflex
sensitivity after central dopaminergic stimulation. Clin-Exp-Pharmacol-Physiol.
1998 Jul; 25(7-8): 624-6; ISSN: 0305-1870.
AUSTRALIA. 1. Stimulation of the mesolimbic dopamine system, by micro-
injection of the substance P analogue [pGlu5,MePhe8,Sar9] substance P (DiMe-
C7) into the ventral tegmental area induced a prolonged increase in blood pressure
and circulating levels of vasopressin. 2. In the present study, this treatment
produced a significant decrease of cardiac baroreflex sensitivity in conscious rats.
After pretreatment with the dopamine receptor antagonist raclopride, central
stimulation failed to produce any changes in baroreflex parameters. 3. The central
dopamine-mediated decrease in baroreflex sensitivity may be involved in
functionally potentiating the circulatory actions of vasopressin.. 0; 0; 0; 0; 0;
33507-63-0; 51-61-6; 77128-69-9; 84225-95-6.
160. van, der Wildt GJ; Bergsma, D. P. Visual field enlargement by neuropsychological
training of a hemianopsia patient. Doc-Ophthalmol. 1997; 93(4): 277-92; ISSN:
0012-4486.
NETHERLANDS. A 58-year old hemianopsia patient was submitted to a two-
fold neuropsychological training in order to enhance visual functions in the
affected part of his visual field. At first, the visual field was measured
perimetrically, to serve as a starting measurement with which after-measurements
could be compared. Then, the first training was started: the border area between
the intact and the defect visual field was being stimulated by small light spots.
The training consisted of repetitive detection threshold measurements. After 27
one-hour sessions, the visual field was being measured again. The visual field
appeared to have been enlarged 5 to 12 degrees in the direction of the affected
hemifield and contrast-sensitivity thresholds to have been decreased almost at
every point in the stimulus-array. Then, a second training started; an eye-
movement training. Again, the border area, now shifted outwards, was stimulated.
This time, the stimulus concerned a short presentation of light (< 200 msec.) after
which the subject, to the best of his abilities had to make an eye-movement to the
perceived stimulus-site. Also, he had to categorize the quality of his perception as
well as the direction in which the stimulus was thought to be perceived. After 30
sessions, the visual field appeared to have 'grown' just a little bit more, but this
seems not to be a significant enlargement. More important, the number of detected
stimuli in the supposed 'blind' area had increased, as had the accuracy of the
localization of the stimuli. Preliminary results of the detection training of a second
subject, also 58 years of age, are presented. Finally, planned actions are discussed.
161. van, der Wildt GJ; Bergsma, D. P. Visual field enlargement by neuropsychological
training of a hemianopsia patient. Doc-Ophthalmol. 1997; 93(4): 277-92; ISSN:
0012-4486.
NETHERLANDS. A 58-year old hemianopsia patient was submitted to a two-
fold neuropsychological training in order to enhance visual functions in the
affected part of his visual field. At first, the visual field was measured
perimetrically, to serve as a starting measurement with which after-measurements
could be compared. Then, the first training was started: the border area between
the intact and the defect visual field was being stimulated by small light spots.
The training consisted of repetitive detection threshold measurements. After 27
one-hour sessions, the visual field was being measured again. The visual field
appeared to have been enlarged 5 to 12 degrees in the direction of the affected
hemifield and contrast-sensitivity thresholds to have been decreased almost at
every point in the stimulus-array. Then, a second training started; an eye-
movement training. Again, the border area, now shifted outwards, was stimulated.
This time, the stimulus concerned a short presentation of light (< 200 msec.) after
which the subject, to the best of his abilities had to make an eye-movement to the
perceived stimulus-site. Also, he had to categorize the quality of his perception as
well as the direction in which the stimulus was thought to be perceived. After 30
sessions, the visual field appeared to have 'grown' just a little bit more, but this
seems not to be a significant enlargement. More important, the number of detected
stimuli in the supposed 'blind' area had increased, as had the accuracy of the
localization of the stimuli. Preliminary results of the detection training of a second
subject, also 58 years of age, are presented. Finally, planned actions are discussed.
162. Wallace, M. T.; Meredith, M. A.; Stein, B. E. Multisensory integration in the
superior colliculus of the alert cat. J-Neurophysiol. 1998 Aug; 80(2): 1006-10;
ISSN: 0022-3077.
UNITED-STATES. The modality convergence patterns, sensory response
properties, and principles governing multisensory integration in the superior
colliculus (SC) of the alert cat were found to have fundamental similarities to
those in anesthetized animals. Of particular interest was the observation that, in a
manner indistinguishable from the anesthetized animal, combinations of two
different sensory stimuli significantly enhanced the responses of SC neurons
above those evoked by either unimodal stimulus. These observations are
consistent with the speculation that there is a functional link among multisensory
integration in individual SC neurons and cross-modality attentive and orientation
behaviors.
163. Wallace, M. T.; Meredith, M. A.; Stein, B. E. Multisensory integration in the
superior colliculus of the alert cat. J-Neurophysiol. 1998 Aug; 80(2): 1006-10;
ISSN: 0022-3077.
UNITED-STATES. The modality convergence patterns, sensory response
properties, and principles governing multisensory integration in the superior
colliculus (SC) of the alert cat were found to have fundamental similarities to
those in anesthetized animals. Of particular interest was the observation that, in a
manner indistinguishable from the anesthetized animal, combinations of two
different sensory stimuli significantly enhanced the responses of SC neurons
above those evoked by either unimodal stimulus. These observations are
consistent with the speculation that there is a functional link among multisensory
integration in individual SC neurons and cross-modality attentive and orientation
behaviors.
164. Watanabe, S.; Kakigi, R.; Koyama, S.; Hoshiyama, M.; Kaneoke, Y. Pain processing
traced by magnetoencephalography in the human brain. Brain-Topogr. 1998 Jun;
10(4): 255-64; ISSN: 0896-0267.
UNITED-STATES. The temporal and spatial processing of pain perception in
human was traced by magnetoencephalography (MEG). We applied a painful
CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated
areas using a single equivalent current dipole (ECD) at each time point, and a brain
electric source analysis (BESA) as a spatio-temporal multiple source analysis
method. The four-source model was found to be the most appropriate; sources 1
and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the
stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the
amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the
stimulation, respectively. Activities in all 4 areas were temporally overlapped.
Activity in the primary sensory cortex (SI) contralateral to the stimulated site was
not identified. Activity in the cingulate cortex was also not clearly identified.
These results are probably due to one or more of the following factors; (1) the
cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are
mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres
interfere with each other. No significant or consistent magnetic fields were
recorded after 500 msec following the stimulation, probably due to the
complicated spatial and temporal overlapping of activities in multiple areas.
165. Watanabe, S.; Kakigi, R.; Koyama, S.; Hoshiyama, M.; Kaneoke, Y. Pain processing
traced by magnetoencephalography in the human brain. Brain-Topogr. 1998 Jun;
10(4): 255-64; ISSN: 0896-0267.
UNITED-STATES. The temporal and spatial processing of pain perception in
human was traced by magnetoencephalography (MEG). We applied a painful
CO2 laser beam to the forearm of 11 normal subjects, and estimated the activated
areas using a single equivalent current dipole (ECD) at each time point, and a brain
electric source analysis (BESA) as a spatio-temporal multiple source analysis
method. The four-source model was found to be the most appropriate; sources 1
and 2 at the secondary sensory cortex (SII) contralateral and ipsilateral to the
stimulation, and sources 3 and 4 at the anterior medial temporal area (probably the
amygdalar nuclei or hippocampal formation) contralateral and ipsilateral to the
stimulation, respectively. Activities in all 4 areas were temporally overlapped.
Activity in the primary sensory cortex (SI) contralateral to the stimulated site was
not identified. Activity in the cingulate cortex was also not clearly identified.
These results are probably due to one or more of the following factors; (1) the
cingulate cortex is too deep, (2) the ECDs generated in the cingulate cortex are
mainly oriented radially, and (3) the ECDs generated in bilateral hemispheres
interfere with each other. No significant or consistent magnetic fields were
recorded after 500 msec following the stimulation, probably due to the
complicated spatial and temporal overlapping of activities in multiple areas.
166. Watanabe, T.; Morimoto, K.; Nakamura, M.; Suwaki, H. Modification of behavioral
responses induced by electrical stimulation of the ventral tegmental area in rats.
Behav-Brain-Res. 1998 Jun; 93(1-2): 119-29; ISSN: 0166-4328.
NETHERLANDS. To investigate the role of the ventral tegmental area (VTA), a
source of the mesolimbic dopaminergic pathway, in paranoid psychosis, a detailed
analysis of the behavioral responses induced by electrical stimulation of the VTA
was made. Abnormal behavior induced by bilateral high-frequency stimulation of
the VTA consisted of two components: forward locomotion and exploration.
Similar responses were obtained when the nucleus accumbens (NAC) or
prefrontal cortex (PFC) were stimulated. The expression of behavioral responses
to stimulation was significantly attenuated by dopamine (DA) receptor or
antagonists, such as haloperidol, YM-09151-2 and SCH23390. These results
indicate that VTA stimulation causes a transient hyperdopaminergic state in the
brain, that resembles psychostimulant-induced abnormal behavior. The effects of
chronic administration of methamphetamine (MAP) on the behavioral responses
to electrical stimulation of the VAT were also investigated. Although an acute
administration of MAP did not affect the behavioral responses to electrical
stimulation of the VTA, chronic treatment with MAP (for 2 weeks) caused a
long-lasting reduction in the electrical threshold for the induction of abnormal
behavior, compared with chronic saline-treated rats. It is suggested that a lasting
enhancement in the behavioral response to stimulation of VTA neurons may
contribute to the etiology of paranoid schizophrenia and amphetamine psychosis..
0; 0; 537-46-2.
167. Williams, S. M.; Goldman Rakic, P. S. Widespread origin of the primate mesofrontal
dopamine system. Cereb-Cortex. 1998 Jun; 8(4): 321-45; ISSN: 1047-3211.
UNITED-STATES. The dopaminergic innervation of the frontal cortex,
commonly implicated in psychiatric and neurological disorders, has traditionally
been associated with a circumscribed midline group of ventral tegmental area
(VTA) neurons. We have employed a combination of retrograde tracing, using
fluorescent dyes, and tyrosine hydroxylase (TH) immunohistochemistry to
amplify knowledge of frontal cortex-projecting dopamine (DA) neurons in non-
human primates. Injections of retrograde fluorochromes were made in areas 46,
8B/6M, 12, 4, 24, and the prelimbic (PL) and infralimbic areas (IL) of the rhesus
monkey. The mesencephalic distribution of neurons exhibiting both retrograde
labeling and TH immunoreactivity or retrograde labeling alone was examined from
the level of the mammillary bodies to the locus coeruleus. DA afferents
innervating the macaque frontal cortex as a whole originate from an unexpectedly
widespread continuum of neurons distributed in the dorsal aspects of all three of
the mesencephalic DA cell groups [A9, A10 and A8; generally corresponding to
the DA cells of the substantia nigra (SN), VTA, and the retrorubral area (RRA)
respectively]. A large number of these retrogradely labeled neurons are non-
dopaminergic. The dorsal frontal cortex (areas 46, BB/6M and 4) receive DA
projections primarily from the full medial-lateral extent of A9 cells dorsal to the
SN pars compacta (i.e. A9 dorsalis), the RRA and to a lesser extent from the A10
parabrachial pigmented nucleus (PBPG) and linear nuclei, the latter of which have
been associated with the mesocortical DA system. In contrast, the ventromedial
PL and IL exhibit a significantly more robust input from the PBPG and midline
linear VTA nuclei than from the lateral groups. The anterior cingulate cortex (area
24) is innervated by a group of DA neurons primarily located between these
laterally and medially concentrated populations. These findings demonstrate a
degree of compartmentalization of the mesofrontal DA system in primates, and
suggest that this projection should no longer be viewed as a unitary midline
system.. 0; 0; 51-61-6; 74749-42-1.
168. Willis, G. L.; Armstrong, S. M. Orphan neurones and amine excess: the functional
neuropathology of Parkinsonism and neuropsychiatric disease. Brain-Res-Brain-
Res-Rev. 1998 Aug; 27(3): 177-242; ISSN: 0165-0173.
NETHERLANDS. The aetiology and treatment of Parkinsonism is currently
conceptualised within a dopamine (DA) deficiency-repletion framework. Loss of
striatal DA is thought to cause motor impairment of which tremor, bradykinaesia
and rigidity are prominent features. Repletion of deficient DA should at least
minimise parkinsonian signs and symptoms. In Section 2, based on extensive pre-
clinical and clinical findings, the instability of this approach to Parkinsonism is
scrutinised as the existing negative findings challenging the DA deficiency
hypothesis are reviewed and reinterpreted. In Section 3 it is suggested that
Parkinsonism is due to a DA excess far from the striatum in the area of the
posterior lateral hypothalamus (PLH) and the substantia nigra (SN). This unique
area, around the diencephalon/mesencephalon border (DCMCB), is packed with
many ascending and descending fibres which undergo functional transformation
during degeneration, collectively labelled 'orphan neurones'. These malformed cells
remain functional resulting in pathological release of transmitter and perpetual
neurotoxicity. Orphan neurone formation is commonly observed in the PLH of
animals and in man exhibiting Parkinsonism. The mechanism by which orphan
neurones impair motor function is analogous to that seen in the diseased human
heart. From this perspective, to conceptualise orphan neurones at the DCMCB as
'Time bombs in the brain' is neither fanciful nor unrealistic [E.M. Stricker, M.J.
Zigmond, Comments on effects of nigro-striatal dopamine lesions, Appetite 5
(1984) 266-267] as the DA excess phenomenon demands a different therapeutic
approach for the management of Parkinsonism. In Section 4 the focus is on this
novel concept of treatment strategies by concentrating on non-invasive,
pharmacological and surgical modification of functional orphan neurones as they
affect adjacent systems. The Orphan neurone/DA excess hypothesis permits a
more comprehensive and defendable interpretation of the interrelationship
between Parkinsonism and schizophrenia and other related disorders. Copyright
1998 Elsevier Science B.V.. 51-61-6.
169. Witton, C.; Talcott, J. B.; Hansen, P. C.; Richardson, A. J.; Griffiths, T. D.; Rees, A.;
Stein, J. F.; Green, G. G. Sensitivity to dynamic auditory and visual stimuli
predicts nonword reading ability in both dyslexic and normal readers. Curr-Biol.
1998 Jul 2; 8(14): 791-7; ISSN: 0960-9822.
ENGLAND. BACKGROUND: Developmental dyslexia is a specific disorder of
reading and spelling that affects 3-9% of school-age children and adults. Contrary
to the view that it results solely from deficits in processes specific to linguistic
analysis, current research has shown that deficits in more basic auditory or visual
skills may contribute to the reading difficulties of dyslexic individuals. These
might also have a crucial role in the development of normal reading skills. Evidence
for visual deficits in dyslexia is usually found only with dynamic and not static
stimuli, implicating the magnocellular pathway or dorsal visual stream as the
cellular locus responsible. Studies of such a dissociation between the processing of
dynamic and static auditory stimuli have not been reported previously.
RESULTS: We show that dyslexic individuals are less sensitive both to particular
rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to
dynamic visual-motion stimuli. There were high correlations, for both dyslexic and
normal readers, between their sensitivity to the dynamic auditory and visual
stimuli. Nonword reading, a measure of phonological awareness believed crucial to
reading development, was also found to be related to these sensory measures.
CONCLUSIONS: These results further implicate neuronal mechanisms that are
specialised for detecting stimulus timing and change as being dysfunctional in
many dyslexic individuals. The dissociation observed in the performance of
dyslexic individuals on different auditory tasks suggests a sub-modality division
similar to that already described in the visual system. These dynamic tests may
provide a non-linguistic means of identifying children at risk of reading failure.
170. Witton, C.; Talcott, J. B.; Hansen, P. C.; Richardson, A. J.; Griffiths, T. D.; Rees, A.;
Stein, J. F.; Green, G. G. Sensitivity to dynamic auditory and visual stimuli
predicts nonword reading ability in both dyslexic and normal readers. Curr-Biol.
1998 Jul 2; 8(14): 791-7; ISSN: 0960-9822.
ENGLAND. BACKGROUND: Developmental dyslexia is a specific disorder of
reading and spelling that affects 3-9% of school-age children and adults. Contrary
to the view that it results solely from deficits in processes specific to linguistic
analysis, current research has shown that deficits in more basic auditory or visual
skills may contribute to the reading difficulties of dyslexic individuals. These
might also have a crucial role in the development of normal reading skills. Evidence
for visual deficits in dyslexia is usually found only with dynamic and not static
stimuli, implicating the magnocellular pathway or dorsal visual stream as the
cellular locus responsible. Studies of such a dissociation between the processing of
dynamic and static auditory stimuli have not been reported previously.
RESULTS: We show that dyslexic individuals are less sensitive both to particular
rates of auditory frequency modulation (2 Hz and 40 Hz but not 240 Hz) and to
dynamic visual-motion stimuli. There were high correlations, for both dyslexic and
normal readers, between their sensitivity to the dynamic auditory and visual
stimuli. Nonword reading, a measure of phonological awareness believed crucial to
reading development, was also found to be related to these sensory measures.
CONCLUSIONS: These results further implicate neuronal mechanisms that are
specialised for detecting stimulus timing and change as being dysfunctional in
many dyslexic individuals. The dissociation observed in the performance of
dyslexic individuals on different auditory tasks suggests a sub-modality division
similar to that already described in the visual system. These dynamic tests may
provide a non-linguistic means of identifying children at risk of reading failure.
171. Xi, Z. X.; Stein, E. A. Nucleus accumbens dopamine release modulation by
mesolimbic GABAA receptors-an in vivo electrochemical study. Brain-Res. 1998
Jul 6; 798(1-2): 156-65; ISSN: 0006-8993.
NETHERLANDS. The role of GABA receptors in regulating the mesolimbic
dopamine (DA) system and drug reinforced behaviors has not been well
characterized. Using fast-cyclic voltammetry, the effects of specific GABA
receptor modulation on DA release in the nucleus accumbens (NAcc) and heroin
self-administration (SA) behavior was investigated. The GABAA agonist
muscimol, administered either intravenously or directly into the ventral tegmental
area (VTA), significantly increased DA release in the NAcc in 7 of the 10 rats
tested. DA release decreased in the remaining three rats; both effects were blocked
by pretreatment with the GABAA receptor antagonist bicuculline. In contrast,
the GABAB agonist baclofen decreased, while 2-OH-saclofen (a GABAB
antagonist) increased DA release in the NAcc. However, when VTA GABAB
receptors were previously activated or inactivated by microinjections of baclofen
or 2-OH-saclofen, systemic injections of muscimol caused an inhibition of NAcc
DA release. These results suggest that GABAA receptors may be co-localized on
both DA neurons and non-DA (GABAergic) interneurons in the VTA, with the
effects of GABAA determined by the net effect of both direct inhibition and
indirect disinhibition of DA neurons. Finally, although a DA releaser, muscimol
was neither self-administered in drug naive rats, nor did it substitute for heroin in
rats previously trained to self-administer heroin, suggesting that GABAA
receptors appear to play a complex role in mediating drug reinforcement,
depending upon the dynamic functional state of GABAA receptors on both
tegmental DA and non-DA neurons. Copyright 1998 Elsevier Science B.V. All
rights reserved.. 0; 0; 0; 1134-47-0; 117354-64-0; 2763-96-4; 51-61-6.
172. Yabe, H.; Tervaniemi, M.; Sinkkonen, J.; Huotilainen, M.; Ilmoniemi, R. J.; Naatanen,
R. Temporal window of integration of auditory information in the human brain.
Psychophysiology. 1998 Sep; 35(5): 615-9; ISSN: 0048-5772.
UNITED-STATES. A deviation in the acoustic environment activates an
automatic change-detection system based on a memory mechanism that builds a
neural trace representing the preceding sounds. The present study revealed that
the auditory-cortex mechanisms underlying this sensory memory integrate
acoustic events over time, producing a perception of a unitary auditory event. We
recorded magnetic responses (MMNm) to occasional stimulus omissions in trains
of stimuli presented at a constant stimulus-onset asynchrony (SOA) that was, in
different blocks, either shorter or longer in duration than the assumed length of the
temporal window of integration. A definite MMNm was elicited by stimulus
omission only with the three shortest SOAs used: 100, 125, and 150 ms, but not
with 175 ms. Thus, 160-170 ms was estimated as the length of the temporal
window used by the central auditory system in integrating successive auditory
input into auditory event percepts.
173. Yabe, H.; Tervaniemi, M.; Sinkkonen, J.; Huotilainen, M.; Ilmoniemi, R. J.; Naatanen,
R. Temporal window of integration of auditory information in the human brain.
Psychophysiology. 1998 Sep; 35(5): 615-9; ISSN: 0048-5772.
UNITED-STATES. A deviation in the acoustic environment activates an
automatic change-detection system based on a memory mechanism that builds a
neural trace representing the preceding sounds. The present study revealed that
the auditory-cortex mechanisms underlying this sensory memory integrate
acoustic events over time, producing a perception of a unitary auditory event. We
recorded magnetic responses (MMNm) to occasional stimulus omissions in trains
of stimuli presented at a constant stimulus-onset asynchrony (SOA) that was, in
different blocks, either shorter or longer in duration than the assumed length of the
temporal window of integration. A definite MMNm was elicited by stimulus
omission only with the three shortest SOAs used: 100, 125, and 150 ms, but not
with 175 ms. Thus, 160-170 ms was estimated as the length of the temporal
window used by the central auditory system in integrating successive auditory
input into auditory event percepts.
174. Yu, J.; Coirini, H.; Kallstrom, L.; Wiesel, F. A.; Johnson, A. E. Differential
modulation of dopamine D1-receptor binding and mRNA expression in the basal
ganglia by the D1-receptor antagonist, SCH-23390. Synapse. 1998 Sep; 30(1): 38-
48; ISSN: 0887-4476.
UNITED-STATES. Dopamine D1-receptor binding in the basal ganglia is
differentially regulated by subtype nonspecific dopamine antagonists such as the
antipsychotic, Fluphenazine. The purpose of the present study was to determine
the relative contributions of D1 and D2 receptor systems in the regulation of basal
ganglia D1-receptor binding. Rats were injected twice daily for 21 days with
saline, the D1-receptor antagonist, SCH-23390, the D2-receptor antagonist,
Raclopride, or both SCH-23390 and Raclopride. Dopamine D1-receptor levels (as
indicated by [125I]SCH-23982 binding) and mRNA expression were measured
using receptor autoradiographic and in situ hybridization histochemical
techniques. [125I]NCQ-298 binding to D2-receptors was also measured as a
positive control for the effects of Raclopride. SCH-23390 administration
independently increased [125I]SCH-23982 binding in a region-dependent manner
with the greatest increases occurring in the entopeduncular nucleus. SCH-23390
also increased D1-receptor mRNA expression in specific striatal subregions
suggesting that increases in binding were related to changes in receptor synthesis.
In addition, Raclopride independently enhanced D2 binding with comparable
increases observed in extrastriatal regions and increases of a lesser magnitude in
the striatum. These data show that the modulation of basal ganglia D1-receptor
binding observed in animals treated with nonselective antagonists is due primarily
to the blockade of D1-receptors. The differential enhancement in basal ganglia D1
binding observed after D1-receptor blockade may be due to anatomical or
phenotypic heterogeneity within the population of striatal D1-receptor
synthesizing neurons. Similarly, the differential enhancement in striatal and
extrastriatal D2-receptor binding may be due to differences in the regulation of
striatal and extrastriatal D2-receptor synthesizing neurons.. 0; 0; 0; 0; 0; 116780-
39-3; 84225-95-6; 87075-17-0.
175. Zhang, J.; Price, J. O.; Graham, D. G.; Montine, T. J. Secondary excitotoxicity
contributes to dopamine-induced apoptosis of dopaminergic neuronal cultures.
Biochem-Biophys-Res-Commun. 1998 Jul 30; 248(3): 812-6; ISSN: 0006-291X.
UNITED-STATES. Dopamine (DA) and related catechols may contribute to
selective degeneration of dopaminergic neurons in the substantia nigra in
Parkinson's disease. To investigate whether DA induces apoptosis of
dopaminergic neurons, we characterized the effects of various concentrations of
exogenous DA on a substantia nigra/neuroblastoma hybrid cell line (MES 23.5 or
MES). The hybrid MES cells were maintained in the presence of 50 microM
glutamate in logarithmic growth on poly-D-lysine-precoated T-75 flasks and
plated either onto petri dishes with glass coverslips for morphological studies or
onto 6-well plates for quantification of apoptosis by flow cytometry. The results
showed that DA exposure (0.5-20 microM) induced time- and dose-dependent
apoptotic cell death of MES cells. To further analyze the mechanism responsible
for DA-mediated apoptosis, we repeated the experiments at 20 microM DA in
the presence or absence of 40 microM nomifensine, a DA re-uptake inhibitor, and
25 microM 2-amino-5-phosphonopentanoic acid (AP5), an N-methyl-D-aspartate
(NMDA) receptor antagonist. The data indicate that both compounds
significantly prevented DA-induced apoptosis of MES cells and that combination
of AP5 and nomifensine provided greater protection against DA toxicity than
AP5 alone. These results suggest for the first time that DA-induced apoptosis in
dopaminergic neurons is partially attributable to increased vulnerability of these
cells to non-toxic levels of excitatory amino acids, i.e., secondary excitotoxicity..
0; 24526-64-5; 25104-18-1; 51-61-6; 76726-92-6.