d-fenfluramine in a rat model of dietary fat-induced obesity.
d-Fenfluramine is an appetite suppressant drug that acts by releasing serotonin from axon terminals and inhibiting its reuptake. S 5B/P1 rats, which are resistant to dietary-fat induced obesity, and Osborne-Mendel rats, which are sensitive, were adapted to ad lib feeding of either a low- or high-fat diet. d-Fenfluramine (10 mg/kg, IP) was injected daily for 12 days. Other than a slightly greater suppression of food intake in Osborne-Mendel rats, there was little difference in response to d-fenfluramine between S 5B/P1 and Osborne-Mendel rats eating the low-fat diet. However, in Osborne-Mendel rats d-fenfluramine completely abolished the excess food intake and weight gain associated with the high-fat diet. Purine nucleotide (GDP) binding on day 13 was higher in S 5B/P1 rats than in Osborne-Mendel rats and was increased by d-fenfluramine in animals of both strains eating the low-fat diet. The high-fat diet increased GDP binding only in S 5B/P1 rats and blocked the fenfluramine-induced increase in GDP binding in both strains. We speculate that d-fenfluramine blocks a feeding reward system stimulated by the high-fat diet.
Fisler
J S
JS
Department of Medicine, School of Medicine, University of Southern California, Los Angeles 90033.
Underberger
S J
SJ
York
D A
DA
Bray
G A
GA
D000818:Animals; D004041:Dietary Fats / Q000008:administration & dosage; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000627:therapeutic use*; D006153:Guanosine Diphosphate / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D051381:Rats; D012701:Serotonin / Q000378:metabolism; D013045:Species Specificity; D013564:Sympathetic Nervous System / Q000187:drug effects; D015430:Weight Gain / Q000187:drug effects
D004041:Dietary Fats; D006153:Guanosine Diphosphate; D005277:Fenfluramine; D012701:Serotonin