Long-term treatment with chlorpromazine and haloperidol but not with sulpiride and clozapine markedly elevates neuropeptide Y-like immunoreactivity in the rat hypothalamus.

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-term treatment with typical neuroleptics. The dopamine D2 agonist quinpirole antagonized the effects of chlorpromazine and haloperidol, but it did not change NPY-LI concentration by itself. Co-administration of the alpha 1 adrenergic antagonist prazosin with quinpirole to chlorpromazine-pretreated rats attenuated the effect of quinpirole but enhanced an increase in NPY-LI content elicited by chlorpromazine. Neither the dopamine D1 antagonist SCH 23390 (1 mg/kg) nor the dopamine D2 antagonist sulpiride (100 mg/kg) administered i.p. for 14 days by itself altered the hypothalamic NPY-LI level, but in combination they increased it. Our results suggest that NPY in hypothalamus may be involved in the mechanism of action of typical non-selective neuroleptics and that the influence of studied drugs on NPY-LI is at least partly mediated by a simultaneous prolonged blockade of both D1 and D2 dopaminergic receptors.