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