Thioperamide, a histamine H-3 receptor antagonist, powerfully suppresses peptide YY-induced food intake in rats

Background: Whether or not peptide YY (PYY)-induced hyperphagia is modified by the histaminergic system in the brain is nor yet known. Methods: We investigated the effect on feeding of intra-cerebroventricular (ICV) administration of a specific histamine H-3 receptor antagonist prior to ICV administration of PW in mts, Results: PW (1, 3, and 10 mu g/10 mu L) strongly induced feeding behavior i n a dose-dependent manner in sated mts. The 4-hour food intake induced by 3 mu g/10 mu L Of PW was equal to that induced by a 16-hour fast. The ICV ad ministration of thioperamide (40.8, 122.4, and 408.5 mu g/10 mu L) did not suppress the 4-hour food intake induced by 16-hour fasting; however; thiope ramide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-mu g dose of PYY. Conclusions: These results suggest that the effect of PYY on appetite is di fferent than that induced by fasting and may involve a histaminergic mechan ism. (C) 1999 Society of Biological Psychiatry.