Evidence for a difference in mechanism of action between fenfluramine- and amphetamine-induced anorexia

Abstract

The influence of drugs, active on 5-hydroxytryptamine (5-HT) mechanisms, has been examined on the anorexigenic activity of fenfluramine and (+)-amphetamine in rats trained to consume their daily food ration during 6 h. Chlorimipramine, which inhibits the re-uptake mechanisms in central 5-HT neurons, and the 5-HT blocking drugs methergoline and methysergide were used. Fenfluramine, 7.5 mg kg−1, and amphetamine, 2.5 mg kg−1, given 1/2 h before feeding reduced the food intake during the following 2 h to approximately 40% compared with control days. Pretreatment with methergoline in the optimal dose (1 mg kg−1) produced only a weak but significant antagonism to amphetamine anorexia, whereas the fenfluramine anorexia was strongly antagonized by methergoline in all doses tested (0.3, 1 and 3 mg kg−1). Methysergide (0.1, 0.3, 1 and 3 mg kg−1) showed no significant antagonism against amphetamine or fenfluramine anorexia. Chlorimipramine produced a strong antagonistic effect to the fenfluramine anorexia, but showed no antagonism against amphetamine. In contrast the highest dose of chlorimipramine (20 mg kg−1) potentiated amphetamine anorexia. The present results together with other evidence discussed support the conclusion that 5-HT mechanisms are involved in fenfluramine anorexia, whereas amphetamine anorexia seems mainly correlated with catecholamine dependent mechanisms.