Synergistic anorectic effect of dehydroepiandrosterone and d-fenfluramine on the obese Zucker rat

Fasted obese, female Zucker rats accustomed to eating a single high fat mea l within 1 h a day were treated with intraperitoneal injections of dehydroe piandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually o r in combination. Caloric intake was measured over a l-h period 2 h after d rug administration, and results compared to that of vehicle-treated control s. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of le ss than or equal to 2 mg/kg d-fen did not affect food intake. Together, how ever, DHEA 50 mg/kg and d-fen less than or equal to 2 mg/kg significantly d ecreased food intake. At doses of greater than or equal to 3 mg/kg d-fen di minished caloric intake by itself, and the addition of DHEA significantly a ugmented this effect. Neurotransmitter levels in select regions of the hypo thalamus of animals treated using a similar drug protocol showed several ch anges in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (S-HIAA). It is hypothesized that DHEA augments the production of sero tonin while d-fenfluramine enhances its release, and together these two act ions may account for the synergistic action of DHEA and d-fenfluramine. (C) 1999 Elsevier Science Inc.