Chronic fenfluramine treatment: effects on body weight, food intake and energy expenditure.

Fenfluramine suppressess the body weight of experimental animals during chronic treatment by a mechanism that is not yet clear. The present research investigated the contributions of fenfluramine-induced alterations in food intake and two components of energy expenditure, resting energy expenditure (REE) and the thermic effect of food (TEF), to maintenance of a lowered body weight in male Long Evans rats. DI-Fenfluramine (20 mg/kg) produced an initial severe anorexia and weight loss. Food intake then increased steadily, reaching control levels by the fourth day of treatment. Tolerance to the anorectic effects of fenfluramine was not complete however -- food intake of fenfluramine-treated rats fell below control levels on 7 of the remaining 20 days of treatment. The body weight of fenfluramine treated rats remained significantly below control levels throughout the entire treatment period, but rose rapidly to control levels following fenfluramine withdrawal. REE was unaffected by fenfluramine treatment. By contrast, fenfluramine treatment significantly altered the TEF. Twenty-four hours after initiation of treatment the TEF of fenfluramine treated animals was higher than that of controls. On the 15th day of drug administration and the first day of fenfluramine withdrawal, however, the TEF of control and treated animals no longer differed. By contrast, on the second day of fenfluramine withdrawal the TEF of fenfluramine treated rats was suppressed to 17% of control levels. These findings suggest that the effect of fenfluramine on body weight involves modulation of both food intake and energy expenditure.