Fenfluramine treatment in female rats accelerates the weight loss associated with activity-based anorexia

Serotonin plays an important role in controlling food intake and regulating body weight. Thus, altered serotonergic function may be involved in the etiology of anorexia nervosa. To investigate this hypothesis, we examined whether activation of the serotonin system increases the severity of activity-based anorexia, an animal model of anorexia nervosa in which food-restricted rats are housed with access to running wheels. This paradigm promotes symptoms of anorexia nervosa, including hypophagia, hyperactivity, and weight loss. Food-restricted rats received injections of a serotonin agonist, fenfluramine, or saline 1.5 h prior to their daily 2-h period of food access. A third saline-injected group was pair-fed to the fenfluramine group. Drug treatment and food restriction were terminated following a 25% weight loss. During food restriction, each group developed symptoms of activity-based anorexia. Although similar reductions in food intake were observed in fenfluramine-treated and pair-fed rats, only fenfluramine-treated rats displayed an accelerated rate of weight loss, relative to saline-treated rats. Thus, some other nonanorexic aspect of fenfluramine, perhaps its influence on metabolism, must underlie the accelerated rate of weight loss in this group. Our results suggest that increased activation of the serotonin system exacerbates the weight loss associated with activity-based anorexia.