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 (POM...

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Veröffentlicht in:	Brain research 2006-05, Vol.1087 (1), p.83-86
Hauptverfasser:	Choi, SuJean, Blake, Valarie, Cole, Sara, Fernstrom, John D.
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Appetite Arcuate Nucleus of Hypothalamus - drug effects Behavior, Animal Biological and medical sciences Body Weight - drug effects Corticotropin-Releasing Hormone - genetics Corticotropin-Releasing Hormone - metabolism Eating - drug effects Feeding. Feeding behavior Fenfluramine Fenfluramine - administration & dosage Fundamental and applied biological sciences. Psychology Gene Expression - drug effects Hypothalamus In Situ Hybridization - methods Male mRNA Neuropeptide Neuropeptide Y - genetics Neuropeptide Y - metabolism Neuropeptides - genetics Neuropeptides - metabolism Pro-Opiomelanocortin - genetics Pro-Opiomelanocortin - metabolism Rat Rats Serotonin Uptake Inhibitors - administration & dosage Time Factors Vertebrates: anatomy and physiology, studies on body, several organs or systems
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Zusammenfassung:	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.
ISSN:	0006-8993 1872-6240
DOI:	10.1016/j.brainres.2006.02.129