Hypothalamic lesions and drug induced anorexia

Four experiments are reported dealing with chemically induced anorexia in animals with hypothalamic lesions. In rats with bilateral lesions of the lateral hypothalamus amphetamine anorexia was markedly diminished while fenfluramine anorexia was significantly enhanced. This finding is consistent with the belief that these two anorexic agents operate through quite separate sites of action: amphetamine acts through the lateral hypothalamus but this zone is not crucial for the mediation of fenfluramine anorexia. The marked similarity shown in the second experiment, between the effectiveness of fenfluramine and 5 hydroxytryptophan in lesioned animals provides further evidence for a serotonergic mechanism in fenfluramine anorexia. The third experiment indicated that the anorexia produced by norfenfluramine, 780SE and compound 2858, was enhanced in animals with lateral hypothalamic lesions. In a further experiment anterior hypothalamic lesions enhanced amphetamine anorexia but had no effect on fenfluramine anorexia. The results of the present study together with previous experiments have now shown that lesions in three separate, but interrelated, hypothalamic sites fail to diminish the anorexic potency of fenfluramine. These findings cast doubt on the notion that fenfluramine anorexia is mediated through a specific hypothalamic site.