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Evidence for a difference in mechanism of action between fenfluramine- and amphetamine-induced anorexia
Authors:S Jespersen  J Scheel-Krüger
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.
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