Inhibition of drug-induced anorexia in rats by methysergide

Iproniazid was found to reduce food consumption in fasting rats. Combined treatment of iproniazid with tryptophan resulted in a significantly greater anorexic action whilst tryptophan alone had no effect on food consumption. Iproniazid treatment was associated with a significant increase in brain 5-hydroxytryptamine (5-HT) concentration but in association with tryptophan higher brain 5-HT concentrations were recorded. The anorexic action of the iproniazid-tryptophan combination was antagonized in a dose-dependent fashion by methysergide. Equivalent levels of anorexia induced by fenfluramine and mazindol were similarly antagonized by methysergide in a dose-related manner. The results suggest a common role of 5-HT in the inhibition of eating behaviour in fasting rats when anorexia is induced by iproniazid, fenfluramine or mazindol, sensitive to a specific 5-HT antagonist.