Effect of continuous infusions of dexfenfluramine on food intake, body weight and brain amines in rats.
The present experiments describe the effects of continuous SC infusion, via osmotic minipump, of dexfenfluramine on food intake and body weight of male and female rats. It was found that the food intake of male rats was reduced by infusions of both 3 and 6 mg/kg/day although tolerance developed within 2-4 days at the lower dose. Further, these rats showed tolerance to an acute anorectic test dose of dexfenfluramine. Body weight loss was sustained by both groups. In older (6-8 mo old) female rats, some of which had previously nursed three litters, the anorectic effects of dexfenfluramine (3 and 6 mg/kg/day) were sustained throughout the 6 day infusion, and weight loss was substantial. The effects did not differ between bred and virgin rats of comparable age. The lower dose of dexfenfluramine produced no depletion of brain serotonin (5HT), although 5HIAA was reduced. Both compounds were depleted by the higher dose. The 3 mg/kg/day dose, in select rat populations, may be a close model for the mode of dexfenfluramine administration to humans.
D000588:Amines / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003692:Delayed-Action Preparations; D004298:Dopamine / Q000378:metabolism; D004435:Eating / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism
D000588:Amines; D003692:Delayed-Action Preparations; D005277:Fenfluramine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D004298:Dopamine; D009638:Norepinephrine