Serotonin (5-HT) plays an important role in controlling food intake and regulating body weight. In addition, clinical studies suggest a possible role for 5-HT in the etiology of anorexia nervosa. Recently, we have examined the effects of pharmacological manipulation of the 5-HT system in female rats exposed to conditions that promote activity-based anorexia (ABA). In this animal model of anorexia nervosa, rats are food restricted (2 h access/day) while given the opportunity to exercise in running wheels. These conditions promote symptoms of anorexia nervosa including hypophagia, hyperactivity, progressive weight loss, and disruptions of the ovarian reproductive cycle. Previously, we demonstrated that increased 5-HT activity increased the weight loss associated with ABA in female rats. Here, we investigated whether decreased 5-HT activity would attenuate symptoms of ABA. Food-restricted female rats received injections of 8-OH-DPAT, a drug that reduces serotonergic neurotransmission, or saline vehicle 40 min prior to food access. During this restricted-feeding phase, food intake was similar between groups; however, 8-OH-DPAT prevented the hyperactivity observed in saline-treated rats. This resulted in less weight loss in 8-OH-DPAT-treated rats, suggesting that decreased activation of the 5-HT system attenuates the development of ABA.