Permanent administration of d-fenfluramine in rats: paradoxical effects.

In order to test the hypothesis of Levitzky that d-fenfluramine (d-F) acts by modifying the ponderal set-point, we compared the effects of a permanent infusion of d-F on food intake and body weight (BW). The effect on the weight persisted as long as the infusion; the clear-cut anorectic effect lasted only a few days. This paradox is compatible with the set-point hypothesis. In rats rendered overweight by insulin treatment, the d-F-induced decrease in BW was approximately four times smaller than in controls. In rats rendered overweight by a cafeteria diet, the decrease in BW was twice as large in permanently cafeteria fed rats as in cafeteria, then, ad lib fed rats. In rats rendered underweight by a restricted chow diet and then returned to an ad lib feeding, the final BW depended only on the doses of d-F (0.6 or 12 mg/kg BW/day), whatever the weight at the beginning of infusion. Thus, the underweight paradigm fits well with the set-point hypothesis; the overweight paradigm fits only partially.