Thioperamide, a histamine H3 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 not yet known. Methods: We investigated the effect on feeding of intracerebroventricular (ICV) administration of a specific histamine H3 receptor antagonist prior to ICV administration of PYY in rats. Results: PYY (1, 3, and 10 μg/10 μL) strongly induced feeding behavior in a dose-dependent manner in sated rats. The 4-hour food intake induced by 3 μg/10 μL of PYY was equal to that induced by a 16-hour fast. The ICV administration of thioperamide (40.8, 122.4, and 408.5 μg/10 μL) did not suppress the 4-hour food intake induced by 16-hour fasting; however, thioperamide produced dose-dependent and strong inhibition of hyperphagia induced by a 3-μg dose of PYY. Conclusions: These results suggest that the effect of PYY on appetite is different than that induced by fasting and may involve a histaminergic mechanism