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 meal within 1 h a day were treated with intraperitoneal injections of dehydroepiandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually or in combination. Caloric intake was measured over a 1-h period 2 h after drug administration, and results compared to that of vehicle-treated controls. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of < or = 2 mg/kg d-fen did not affect food intake. Together, however, DHEA 50 mg/kg and d-fen < or = 2 mg/kg significantly decreased food intake. At doses of > or = 3 mg/kg d-fen diminished caloric intake by itself, and the addition of DHEA significantly augmented this effect. Neurotransmitter levels in select regions of the hypothalamus of animals treated using a similar drug protocol showed several changes in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (5-HIAA). It is hypothesized that DHEA augments the production of serotonin while d-fenfluramine enhances its release, and together these two actions may account for the synergistic action of DHEA and d-fenfluramine.
Gillen
G
G
Department of Medicine, Louisiana State University Medical Center, New Orleans 70112, USA.
Porter
J R
JR
Svec
F
F
D000704:Analysis of Variance; D000818:Animals; D001066:Appetite / Q000187:drug effects*; D001067:Appetite Depressants / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000032:analysis / Q000502:physiology; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D011924:Rats, Zucker; D018490:Serotonin Agents / Q000494:pharmacology*
D001067:Appetite Depressants; D018377:Neurotransmitter Agents; D018490:Serotonin Agents; D005277:Fenfluramine; D003687:Dehydroepiandrosterone