PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “EXTRAPYRAMIDAL TRACTS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 541 records · Page 30Linked to original sources
PubMed1995

Differential distribution of N-acetylaspartylglutamate and N-acetylaspartate immunoreactivities in rat forebrain.

Contradictory immunohistochemical data have been reported on the localization of N-acetylaspartylglutamate in the rat forebrain, using different carbodiimide fixation protocols and antibody purification methods. In one case, N-acetylaspartylglutamate immunoreactivity was observed in apparent interneurons throughout all allocortical and isocortical regions, suggesting possible colocalization with GABA. In another case, strong immunoreactivity was observed in numerous pyramidal cells in neocortex and hippocampus, suggesting colocalization with glutamate or aspartate. Reconciling these disparate findings is crucial to understanding the role of N-acetylaspartylglutamate in nervous system function. Antibodies to N-acetylaspartylglutamate and a structurally related molecule, N-acetylaspartate, were purified in stages, and their cross-reactivities with protein conjugates of N-acetylaspartylglutamate and N-acetylaspartate were monitored at each stage by solid-phase immunoassay. Reduction of the cross-reactivity of the anti-N-acetylaspartylglutamate antibodies of N-acetylaspartate-protein conjugates to about 1% eliminated significant staining of most pyramidal neurons in the rat forebrain. Utilizing highly purified antibodies, the distributions of N-acetylaspartylglutamate and N-acetylaspartate were examined in several major telencephalic and diencephalic regions of the rat, and were found to be distinct. N-acetylaspartylglutamate-immunoreactivity was observed in specific neuronal populations, including many groups thought to use GABA as a neurotransmitter. Among these were the globus pallidus, ventral pallidum, entopeducular nucleus, thalamic reticular nucleus, and scattered non-pyramidal neurons in all layers of isocortex and allocortex. N-acetylaspartate-immunoreactivity was more broadly distributed than N-acetylaspartylglutamate-immunoreactivity in the rat forebrain, appearing strongest in many pyramidal neurons. Although N-acetylaspartate-immunoreactivity was found in most neurons, it exhibited a great range of intensities between different neuronal types.

Amygdala↗
PubMed1991

Antipsychotic-like profile of combined treatment with raclopride and 8-OH-DPAT in the rat: enhancement of antipsychotic-like effects without catalepsy.

The administration of the 5-HT1A agonist 8-OH-DPAT, 0.1 mg kg-1 sc-20 min, produced a moderate suppression of conditioned avoidance behavior (60% of controls) in the rat. This effect, however, was not seen after administration of higher doses, 0.4 and 1.6 mg kg-1 sc. The number of intertrial crosses were not affected by the lower dose but significantly increased by administration of the two higher doses of 8-OH-DPAT. The dopamine D2 receptor blocking agent raclopride, 0.05 mg kg-1, by itself did not suppress the avoidance behavior, but in combination with 8-OH-DPAT produced suppression of avoidance behavior (30% of controls) as well as intertrial crosses. Open field locomotor activity was suppressed by raclopride, 0.1 mg kg-1 sc, or by 8-OH-DPAT, 0.1 mg kg-1 sc. The combined treatment produced a further suppression of locomotor activity and a marked increase in "immobility" (stationary movements). Treadmill locomotion, however, was not affected by either compound by itself, whereas the combined treatment impaired treadmill performance. Suppression of treadmill performance by a higher dose of raclopride, 0.4 mg kg-1 sc, was not altered by the additional treatment with 8-OH-DPAT, 0.1 mg kg-1. In contrast to the additive effects of 8-OH-DPAT and raclopride on conditioned avoidance behavior, open field locomotion and treadmill performance, the catalepsy produced by raclopride, 16 mg kg-1 was completely antagonised by treatment with 8-OH-DPAT 0.1 mg kg-1. Taken together, the present findings demonstrate strong interactions between a 5-HT agonist and a DA D2 antagonist on some critical tests for antipsychotic-like actions and extrapyramidal motor effects in rats, and suggest new possibilities in the search for new antipsychotic drugs with higher clinical efficacy and less extrapyramidal side effects.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1979

Extrapyramidal side effects and increased serum prolactin following fluoxetine, a new antidepressant.

Fluoxetine (Lilly 110140) is a potent, specific serotonin (5-HT) uptake blocker which is being tested in man for antidepressant activity. One of 9 depressed patients receiving this drug developed a dystonic reaction, parkinsonian rigidity, and increased serum prolactin levels, all signs of decreased dopaminergic activity. Homovanillic acid levels also decreased in the cerebrospinal fluid of this subject. We postulate that fluoxetine, via the increase in 5-HT activity resulting from 5-HT uptake blockade, inhibited both the nigro-striatal and tubero-infundibular dopaminergic neurons. These results provide additional evidence for a linkage between serotonergic and dopaminergic neurons in man.

Adult↗
PubMed1995

MK801 induces late regional increases in NMDA and kainate receptor binding in rat brain.

We have previously shown that a single dose of PCP produces a dose-related increase in NMDA-sensitive 3H-glutamate binding in CA1 of hippocampus 24 hours later, and some regional changes in kainate binding. Here we report that dizocilpine (MK 801) (0.1 mg/kg and 1 mg/kg), a selective agonist at the PCP receptor and a noncompetitive antagonist of NMDA, produces a similar increase in NMDA-sensitive glutamate and kainate receptor binding in hippocampus 24 hours after a dose. These observations support the conclusion that blockade of glutamate-mediated transmission at the NMDA receptor selectively increases NMDA-sensitive glutamate receptor binding in CA1 of hippocampus and kainate binding in CA3 and dentate gyrus at putatively delayed time points. Several additional areas outside of hippocampus also showed receptor changes at 24 hours after MK801.

Animals↗
PubMed1987

Neurogenic stuttering.

According to reports in the literature and our own observations, which are reported in this paper, acquired stuttering may occur in conjunction with focal or diffuse damage to the central nervous system. When the lesion is focal, it may be in the right or in the left hemisphere. When the left hemisphere is injured, acquired stuttering may be concomitant with aphasia. Indeed, in some cases the stutter-like repetitions appear to be an integral part of the aphasic syndrome. In other cases, on the contrary, the two disorders seem to be relatively independent of one another. Occasionally, stuttering is the only observable disorder in the linguistic-cognitive sphere.

Aged↗
PubMed1994

Savoxepine fails to selectively influence glucose metabolism in the rat limbic system.

The [14C]-2-deoxyglucose method was used to map the in vivo metabolic response of glucose to savoxepine, a novel tetracyclic cyano-dibenzoxepino-azepine. Savoxepine is reported to have higher affinity for dopamine (DA) receptors in the hippocampus than in the striatum and hence should have dose-dependent, anatomically selective actions. Two doses of savoxepine (0.05 mg/kg and 0.5 mg/kg) were compared with haloperidol (1 mg/kg) to test the hypothesis that low doses of savoxepine would display a selective action on limbic brain areas. Results failed to show that low dose savoxepine selectively modifies glucose utilization in the limbic system as previous biochemical studies suggested. In fact, low doses of the drug displayed a potent activity quite similar to haloperidol in effect and localization. The low dose did not produce significantly altered glucose metabolism in the nucleus accumbens or in the lateral habenular nucleus as observed with most other neuroleptics, suggesting a lack of antipsychotic action at this dose. Our findings demonstrate the difficulty of designing a neuroleptic with a preferential blockade of limbic DA receptors and point to the need for functional assessment of regional receptor binding differences.

Animals↗
PubMed1995

Catalepsy as a rodent model for detecting antipsychotic drugs with extrapyramidal side effect liability.

The predictive validity of catalepsy as a rodent model for detecting the extrapyramidal side effects (EPS) of antipsychotic drugs was recently questioned when the novel antipsychotic savoxepine produced little catalepsy in rodents while producing significant EPS in schizophrenic patients. Because catalepsy is viewed as an important model for predicting EPS, we decided to re-evaluate the effects of savoxepine. Savoxepine, clozapine, haloperidol, olanzapine, ORG 5222, raclopride, and risperidone were examined in two tests for catalepsy (grid and bar tests) in male Sprague-Dawley rats. The ability to antagonize amphetamine-induced hypermotility was also examined, since this measure is believed to predict clinical efficacy. With the exception of clozapine, all drugs produced dose-dependent catalepsy in both tests. For each drug, the minimum effective dose for producing catalepsy was greater than or equal to the ED50 for antagonizing amphetamine-induced hyperactivity (defined as the dose producing a 50% reduction in hyperactivity). Clozapine resulted in the widest separation of effective doses in the catalepsy and activity models. Raclopride produced the next largest separation while the remaining drugs resulted in only a one- or two-fold dose separation between the two behavioral tests. The results with haloperidol and clozapine are consistent with the clinical effects of these drugs (severe versus mild EPS). The ratios of effective doses in catalepsy and activity for the remaining novel drugs are also consistent with preliminary clinical findings indicating some EPS with each of these compounds. Thus, catalepsy remains a suitable rodent model for detecting compounds with EPS liability in humans.

Amphetamine↗
PubMed2003

[Electrophysiological impairment profile of patients with Wilson's disease].

In addition to hepatic and extrapyramidal motor clinical symptoms, Wilson's disease patients also exhibit subclinical disorders of other central nervous pathways. In this study, an impairment profile is described by means of eight electrophysiological tests (EAEP, MSEP, TSEP, T-VEP, MEP, EEG, heart frequency variability, and SSR) for 37 patients (28 with neurological, nine with tnon-neurological form) undergoing long-term drug therapy. The occurrence in 64.3% of a delayed wave III and/or IPL III-V prolongation in patients with the neurological form makes pathological FAEP the most common form of the disorder, followed by disorders in MSEP, TSEP, MEP, and T-VEP. Patients with the non-neurological form usually have normal values, although latency prolongations occur in isolated cases. The range of evoked potential findings is characterised primarily by latency prolongations, i.e. a demyelinising impairment type, and significant losses of potential hardly occur (except in the MEP). The electrophysiological impairment profile does not include EEG changes or vegetative disorders.

Autonomic Nervous System Diseases↗
PubMed1997

Effects of clozapine, thioridazine, risperidone and haloperidol on behavioral tests related to extrapyramidal motor function.

Evidence indicates that the antipsychotic drug clozapine has a low propensity for the induction of extrapyramidal motor symptoms, and also that clozapine has therapeutic effects in patients with idiopathic Parkinson's disease. Because tacrine-induced tremulous jaw movements in rats have been suggested as a possible model of extrapyramidal motor dysfunctions, including parkinsonian tremor, the present work was undertaken to investigate the effects of clozapine on tremulous jaw movements. Clozapine decreased tacrine-induced tremulous jaw movements in a dose-related manner, with an ED50 of approximately 3.3 mg/kg. In order to determine the relative potency of this effect compared to other behavioral effects of clozapine, suppression of lever pressing was also studied. Clozapine reduced lever pressing in a dose-related manner, with an ED50 of approximately 5.4 mg/kg. This indicates that clozapine suppressed jaw movements at or below the doses required for suppression of lever pressing. In contrast, the typical antipsychotic drug haloperidol failed to suppress tacrine-induced tremulous jaw movements in doses up to 1.0 mg/kg, which is about 11-fold higher than the ED50 for suppression of lever pressing with that drug. Thioridazine and risperidone also suppressed tremulous jaw movements in roughly the same dose range at which lever pressing was reduced. It is possible that the suppression of tacrine-induced tremulous jaw movements by clozapine in rats is related to the unique behavioral and motor effects of clozapine. The ratio of potencies of these effects (i.e., suppression of tremulous jaw movements versus suppression of lever pressing) could be used as a behavioral procedure for assessing clozapine-like activity in novel compounds.

Animals↗
PubMed1998

The effects of the atypical antipsychotic amperozide on vacuous jaw movements in rats: a novel dose response profile.

Classic neuroleptic drugs produce a syndrome of vacuous jaw movements in rats, and this syndrome has been offered as an animal model of early onset extrapyramidal side effects. The atypical antipsychotics do not produce elevations in vacuous jaw movements, or do so only at very high doses. The purpose of the present study was to determine the impact of the putative antipsychotic, amperozide, on vacuous jaw movements in rats. Groups of rats received daily injections of haloperidol (0.2, 0.4, or 0.8 mg/kg), clozapine (2.0, 4.0, 8.0 mg/kg), amperozide (2.0, 4.0, 8.0 mg/kg) or vehicle for 4 weeks. Once per week, rats were observed for the presence of vacuous jaw movements. Haloperidol increased vacuous jaw movements with increasing doses. Clozapine only produced elevations in vacuous jaw movements at the highest dose. In contrast, increasing doses of amperozide resulted in decreasing vacuous jaw movements for this portion of the dose-response curve. This is the first report of the effect of amperozide on vacuous jaw movements and results are discussed in terms of a potentially unique behavioral profile with respect to this behavior.

Analysis of Variance↗
PubMed2002

Mini-review: multiple developmental forms of parkinsonism. The basis for further research as to the pathogenesis of parkinsonism.

A range of extrapyramidal disturbances have been reported in children following early brain damage. In adults, damage to the basal ganglia can elicit abnormal motor activity in either direction; it would seem reasonable that the same would apply to damage occurring at an earlier developmental stage. The Viennese paediatrician Widhalm described a hypokinetic/parkinsonoid syndrome ("infantile hypokinetic-hypertonic syndrome with Parkinson symptomatic") presented by a significant minority of the children with extrapyramidal movement disturbances, corresponding to the mild rigid-akinetic type of Parkinson's disease. In contrast to classical parkinsonism, but consistent with some forms of post-encephalitic parkinsonism, the syndrome was reversible, although only after L-DOPA therapy. Widhalm's observation that at least one form of childhood parkinsonism can be cured with L-DOPA also suggests that the amino acid plays a more active role than mere replacement therapy in children, perhaps also acting as a neurotrophic agent. It is proposed that environmental factors, including viral and risk factors associated with pregnancy and birth, together with genetically determined lability, may increase the incidence of early hypokinesia/parkinsonism in particular and of Parkinson's disease in later life by disturbing the immature basal ganglia at critical developmental stages. The spectrum disorder of Parkinson's disease thereby occurs as a number of various etiopathologically distinct syndrome subtypes, including early onset developmental forms caused by in utero or early post partum trauma.

Basal Ganglia↗
PubMed1994

Effects of dopamine partial-agonist aminoergolines on dopamine metabolism in limbic and extrapyramidal regions of rat brain.

The aminoergolines SDZ-208-911, -208-912, and -212-327, weak partial D2 agonists with agonist/antagonist properties, are proposed as potential atypical antipsychotic agents with limited risk of extrapyramidal effects or hyperprolactinemia. The in vivo effects on dopamine (DA) metabolism in limbic (accumbens) and extrapyramidal (striatum) regions of rat brain were evaluated by measuring the accumulation of L-dihydroxyphenylalanine (DOPA) after inhibiting decarboxylation alone ("open-loop" model) or with added gamma-butyrolactone (GBL, autoreceptor model). All three aminoergolines markedly increased DOPA in both regions, dose-dependently, with only minor decreases when GBL was included, and so evidently lack appreciable agonist activity at D2-like autoreceptors and resemble typical neuroleptics in stimulating DA synthesis, without regional selectivity.

4-Butyrolactone↗