Tolerance to the anorectic effect of dexfenfluramine in rats: role of serotonin, cholecystokinin, and neuropeptide Y.
Tolerance to the anorectic effect of dexfenfluramine (DFEN) is shown in rats treated either chronically with low doses or once with a high dose of the agent. Rats given DFEN regimens that result in complete loss of DFEN anorexia showed no change in the anorexia caused by peripheral injection of cholecystokinin (CCK). The orexigenic effects of metergoline and neuropeptide Y were also unaltered as a function of DFEN pretreatment. Both the magnitude and duration of tolerance to a test dose of DFEN seemed to depend, in part, upon contingent (situational) factors, and were independent of whether brain serotonin (5-HT) measures were either unaffected or decreased by the DFEN pretreatment (low and high doses, respectively).
Rowland
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NE
Department of Psychology, University of Florida, Gainesville 32611-2065.
D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D004361:Drug Tolerance; D004435:Eating / Q000187:drug effects; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D005508:Food Deprivation; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D009478:Neuropeptide Y / Q000494:pharmacology*; D017374:Paroxetine / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000502:physiology*; D015431:Weight Loss / Q000187:drug effects
D001067:Appetite Depressants; D009478:Neuropeptide Y; D008711:Metergoline; D005277:Fenfluramine; D012701:Serotonin; D017374:Paroxetine; D002766:Cholecystokinin