GLUTAMATE-DECARBOXYLASE MESSENGER-RNA IN RAT PALLIDUM - COMPARISON OFTHE EFFECTS OF HALOPERIDOL, CLOZAPINE AND COMBINED HALOPERIDOL-SCOPOLAMINE TREATMENTS

Citation
Jm. Delfs et al., GLUTAMATE-DECARBOXYLASE MESSENGER-RNA IN RAT PALLIDUM - COMPARISON OFTHE EFFECTS OF HALOPERIDOL, CLOZAPINE AND COMBINED HALOPERIDOL-SCOPOLAMINE TREATMENTS, Neuroscience, 66(1), 1995, pp. 67-80
Citations number
69
Categorie Soggetti
Neurosciences
Journal title
ISSN journal
03064522
Volume
66
Issue
1
Year of publication
1995
Pages
67 - 80
Database
ISI
SICI code
0306-4522(1995)66:1<67:GMIRP->2.0.ZU;2-O
Abstract
We have investigated the effects of neuroleptic treatments which do, o r do not, induce catalepsy on the level of expression of glutamate dec arboxylase, the rate limiting enzyme in GABA synthesis, in efferent ne urons of the pallidum in adult rats. Different regimens of haloperidol (1 mg/kg s.c., three, seven or 14 days; 2 mg/kg, s.c., 10 days) induc ed catalepsy in a majority of rats and increased glutamate decarboxyla se messenger RNA levels in the globus pallidus (external pallidum) in those rats exhibiting catalepsy. Levels of glutamate decarboxylase mes senger RNA were also increased in the entopeduncular nucleus (internal pallidum), but only after 14 days of treatment with haloperidol. The atypical antipsychotic clozapine (seven days, 20 mg/kg, s.c.), which d id not induce catalepsy, slightly decreased glutamate decarboxylase me ssenger RNA levels in the globus pallidus. When co-administered with h aloperidol (seven days, 1 mg/kg s.c.), the muscarinic antagonist scopo lamine (1 mg/kg, s.c.) completely blocked both haloperidol-induced cat alepsy and increases in glutamate decarboxylase messenger RNA levels i n the globus pallidus. In contrast, scopolamine was not able to block increased glutamate decarboxylase and enkephalin messenger RNA express ion induced by haloperidol in the striatum. These results reveal a goo d correlation between increases in glutamate decarboxylase messenger R NA levels in the globus pallidus and catalepsy after these drug treatm ents and suggest that anticholinergic blockade of the behavioral and m olecular effects of neuroleptics may involve non-striatal mechanisms.