Weight cycling alters the effects of D-fenfluramine on susceptibility to activity-based anorexia.

It has been proposed that anorexia nervosa (AN) is treatable with serotonergic (5-HT) agonists. It seems paradoxical to treat a disorder characterized by reduced food intake with appetite suppressants. The effects of the indirect-acting 5-HT agonist D-fenfluramine on activity-based anorexia (ABA) were investigated, coincident with ABA (experiment 1), and after tolerance and weight cycling (experiment 2). Rats were chronically infused with D-fenfluramine by using subcutaneous mini-pumps and then tested for susceptibility to ABA (22.5 h free running wheel access, 1.5 h access to food). Concurrent D-fenfluramine increased the risk of ABA by decreasing food consumption. Conversely, D-fenfluramine reduced the incidence of ABA in tolerant rats with a history of weight cycling. Therefore, the effects of D-fenfluramine depend on whether drug administration coincides with ABA or whether tolerance and weight cycling precede ABA onset. The results were related to the metabolic effects of weight cycling and the treatment of anorexia nervosa.