Effects of chronic fenfluramine administration on hypothalamic neuropeptide mRNA expression.
Appetite suppressants lose efficacy when given chronically; the mechanisms are unknown. We gave male rats once-daily dl-fenfluramine (dl-FEN, 5 mg/kg, i.p.) injections for 15 days and measured mRNA expression of corticotropin releasing factor (CRF), neuropeptide Y (NPY) and proopiomelanocortin (POMC) in hypothalamic neurons on days 1, 2 and 15. dl-FEN decreased food intake on days 1-2 but not on day 15. The drug increased CRF mRNA and decreased NPY mRNA on days 1-2; on day 15, NPY mRNA was normal, but CRF mRNA remained elevated. No changes occurred in POMC mRNA. Thus, only the NPY mRNA response to dl-FEN correlated with changes in food intake over time in a manner consistent with the known effects of NPY on food intake.
Choi
Sujean
S
Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213, USA. choisj@pitt.edu
Blake
Valarie
V
Cole
Sara
S
Fernstrom
John D
JD
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000187:drug effects*; D001522:Behavior, Animal; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005277:Fenfluramine / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D011333:Pro-Opiomelanocortin / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage*; D013997:Time Factors
D003346:Corticotropin-Releasing Hormone; D005277:Fenfluramine; D009478:Neuropeptide Y; D009479:Neuropeptides; D011333:Pro-Opiomelanocortin; D017367:Selective Serotonin Reuptake Inhibitors