Glutamate decarboxylase messenger RNA in rat pallidum: comparison of the effects of haloperidol, clozapine and combined haloperidol-scopolamine treatments.
We have investigated the effects of neuroleptic treatments which do, or do not, induce catalepsy on the level of expression of glutamate decarboxylase, the rate limiting enzyme in GABA synthesis, in efferent neurons 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) induced catalepsy in a majority of rats and increased glutamate decarboxylase messenger RNA levels in the globus pallidus (external pallidum) in those rats exhibiting catalepsy. Levels of glutamate decarboxylase messenger 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 did not induce catalepsy, slightly decreased glutamate decarboxylase messenger RNA levels in the globus pallidus. When co-administered with haloperidol (seven days, 1 mg/kg s.c.), the muscarinic antagonist scopolamine (1 mg/kg, s.c.) completely blocked both haloperidol-induced catalepsy and increases in glutamate decarboxylase messenger RNA levels in the globus pallidus. In contrast, scopolamine was not able to block increased glutamate decarboxylase and enkephalin messenger RNA expression induced by haloperidol in the striatum. These results reveal a good correlation between increases in glutamate decarboxylase messenger RNA levels in the globus pallidus and catalepsy after these drug treatments and suggest that anticholinergic blockade of the behavioral and molecular effects of neuroleptics may involve non-striatal mechanisms.
Delfs
J M
JM
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Anegawa
N J
NJ
Chesselet
M F
MF
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced; D003024:Clozapine / Q000494:pharmacology*; D004347:Drug Interactions; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005917:Globus Pallidus / Q000187:drug effects / Q000201:enzymology*; D005968:Glutamate Decarboxylase / Q000096:biosynthesis* / Q000235:genetics; D006220:Haloperidol / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology*
D012333:RNA, Messenger; D012601:Scopolamine; D005968:Glutamate Decarboxylase; D003024:Clozapine; D006220:Haloperidol