d-Fenfluramine and self-stimulation: loss of inhibitory effect in underweight rats

The question addressed is whether or not physiological factors associated with body weight, are necessary for serotonergic inhibition of feeding reward. Six rats received the serotonergic drug d-fenfluramine (d-FEN 1.5 and 2.5 mg/kg IP) while they electrically self-stimulated a perifornical lateral hypothalamic (PfLH) site that would induce feeding. As a control, self-stimulation was alternated with stimulation-escape. Both were measured at normal body weight, then at 80% body weight, then normal weight again. Three results were significant. 1) d-FEN markedly suppressed self-stimulation at normal body weight. 2) Self-stimulation rate increased when the animals were put on a diet that reduced body weight to 80% of normal. 3) At this low body weight, d-FEN no longer had any effect on self-stimulation. The results suggest that some correlate of normal food intake or body weight is necessary for serotonergic inhibition of the PfLH feeding-reward system. Possible explanations for fenfluramine's loss of effect at low weight are discussed.