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.