title: 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.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center Utrecht, Universtiteitsweg 100, 3584 CG Utrecht, The Netherlands.
authors.forename: J J G
authors.initials: JJ
authors.lastname: Hillebrand
authors.forename: A C M
authors.initials: AC
authors.lastname: Heinsbroek
authors.forename: M J H
authors.initials: MJ
authors.lastname: Kas
authors.forename: R A H
authors.initials: RA
authors.lastname: Adan
mesh_terms: D000818:Animals; D000855:Anorexia / Q000209:etiology / Q000503:physiopathology*; D001067:Appetite Depressants / Q000494:pharmacology*; D004327:Drinking Behavior / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects*; D005260:Female; D005277:Fenfluramine / Q000494:pharmacology*; D017403:In Situ Hybridization; D009043:Motor Activity; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D014867:Water
chemical_list: D001067:Appetite Depressants; D014867:Water; D005277:Fenfluramine