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.
Obuchowicz
E
E
Department of Clinical Pharmacology, Silesian University School of Medicine, Katowice, Poland.
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines / Q000494:pharmacology; D002746:Chlorpromazine / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D005786:Gene Expression Regulation / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis* / Q000235:genetics; D011224:Prazosin / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors; D013469:Sulpiride / Q000494:pharmacology*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D019257:Quinpirole; D013469:Sulpiride; D003024:Clozapine; D006220:Haloperidol; D002746:Chlorpromazine; D011224:Prazosin