LONG-TERM TREATMENT WITH CHLORPROMAZINE AND HALOPERIDOL BUT NOT WITH SULPIRIDE AND CLOZAPINE MARKEDLY ELEVATES NEUROPEPTIDE Y-LIKE IMMUNOREACTIVITY IN THE RAT HYPOTHALAMUS
E. Obuchowicz, LONG-TERM TREATMENT WITH CHLORPROMAZINE AND HALOPERIDOL BUT NOT WITH SULPIRIDE AND CLOZAPINE MARKEDLY ELEVATES NEUROPEPTIDE Y-LIKE IMMUNOREACTIVITY IN THE RAT HYPOTHALAMUS, Neuropeptides, 30(5), 1996, pp. 471-478
Male Wistar rats were injected intraperitoneally with chlorpromazine (
2 or 10 mg/kg), haloperidol (0.5 or 2 mg/kg), sulpiride (50 or 100 mg/
kg) or clozapine (10 or 25 mg/kg) once, for 14 or 28 consecutive days.
Hypothalamic neuropeptide Y-like (NPY-like) immunoreactivity (NPY-LI)
was determined 24 h after the last dose of the neuroleptic and on the
eighth day after drug withdrawal following a 1 month administration.
A marked increase in the NPY-LI level was observed only after long-ter
m treatment with typical neuroleptics. The dopamine D-2 agonist quinpi
role antagonized the effects of chlorpromazine and haloperidol, but it
did not change NPY-LI concentration by itself. Co-administration of t
he alpha(1) adrenergic antagonist prazosin with quinpirole to chlorpro
mazine-pretreated rats attenuated the effect of quinpirole but enhance
d an increase in NPY-LI content elicited by chlorpromazine. Neither th
e dopamine D-1 antagonist SCH 23390 (1 mg/kg) nor the dopamine D-2 ant
agonist sulpiride (100 mg/kg) administered i.p. for 14 days by itself
altered the hypothalamic NPY-LI level, but in combination they increas
ed it. Our results suggest that NPY in hypothalamus may be involved in
the mechanism of action of typical non-selective neuroleptics and tha
t the influence of studied drugs on NPY-LI is at least partly mediated
by a simultaneous prolonged blockade of both D-1 and D-2 dopaminergic
receptors.