Evidence that d-fenfluramine anorexia is mediated by 5-HT1 receptors

Abstract

The effects of eight serotonin (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine (3.0 mg/kg, IP) were examined in a test of sweet mash consumption, using non-deprived male rats. d-Fenfluramine's effect was attenuated by the mixed 5-HT1/5-HT2 receptor antagonists, methiothepin and metergoline; by the 5-HT2 receptor antagonist ritanserin; and by (+/-)cyanopindolol, a mixed 5-HT1A/5-HT1B receptor antagonist. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonists ketanserin and ICI 169 369; the 5-HT3 receptor antagonist ICS 205 930; or by xylamidine, a peripheral 5-HT receptor antagonist. In this feeding model, none of the 5-HT antagonists, when tested alone, had any effect to increase palatable food consumption. The pattern of results obtained strongly suggest that central 5-HT1 receptors play an important role in the mediation of d-fenfluramine-induced anorexia.