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The appetite suppressant d-fenfluramine reduces water intake, but not food intake, in activity-based anorexia.

Abstract
Biochemical, genetic and imaging studies support the involvement of the serotonin (5-HT) system in anorexia nervosa. Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa, and combines scheduled feeding with voluntary running wheel activity (RWA). We investigated the effect of d-fenfluramine (d-FEN) treatment on development and propagation of ABA. d-FEN is an appetite suppressant and acts on 5-HT(2C) receptors that are located on pro-opiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus. Since stimulation activation of the melanocortin system stimulates ABA, we hypothesized that d-FEN treatment enhances the development and propagation of ABA. Rats were exposed to the ABA model and chronically infused with d-FEN. Unexpectedly, d-FEN-treated ABA rats did not reduce food intake or increase wheel running as compared with vehicle-treated ABA rats. Furthermore d-FEN treatment did not affect body weight loss, hypothalamus-pituitary-adrenal axis activation, or starvation-induced hypothermia in ABA rats. POMC mRNA levels in d-FEN-treated rats were not different from vehicle-treated rats after one week of exposure to the ABA paradigm. However, d-FEN-treated ABA rats showed hypodypsia and increased plasma osmolality and arginine-vasopressin expression levels in the hypothalamus. We conclude that d-FEN treatment does not enhance ABA under the experimental conditions of this study, but strongly reduces water intake in ABA rats.
AuthorsJ J G Hillebrand, A C M Heinsbroek, M J H Kas, R A H Adan
JournalJournal of molecular endocrinology (J Mol Endocrinol) Vol. 36 Issue 1 Pg. 153-62 (Feb 2006) ISSN: 0952-5041 [Print] England
PMID16461935 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Appetite Depressants
  • Water
  • Fenfluramine
Topics
  • Animals
  • Anorexia (etiology, physiopathology)
  • Appetite Depressants (pharmacology)
  • Drinking Behavior (drug effects)
  • Energy Intake (drug effects)
  • Female
  • Fenfluramine (pharmacology)
  • In Situ Hybridization
  • Motor Activity
  • Radioimmunoassay
  • Rats
  • Rats, Wistar
  • Water

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