The BDNF Val66Met Polymorphism Does Not Increase Susceptibility to Activity-Based Anorexia in Rats.

Abstract

Simple SummaryGenetic animal models are a valuable tool for understanding how human pathologies develop. The type of animal model chosen is important for uncovering effects specific to certain behaviours and neurobiological functions. A polymorphism in the brain-derived neurotrophic factor (BDNF) has been linked with various clinical conditions in human subjects and with mouse models of anorectic behaviour. This study investigated for the first time the role of the BDNF Val66Met allelic substitution in a rat model of anorexia nervosa (AN), known as activity-based anorexia (ABA). Contrary to reports of altered BDNF signaling in patients with AN and increased anorectic behaviour in a mouse model containing the same allelic variation, it showed that 66Met did not alter susceptibility to weight loss or aspects of energy balance, including feeding and exercise in the rat model. It highlights the need to consider species–specific differences when evaluating animal models of human pathologies.Brain-derived neurotrophic factor (BDNF) is abundantly expressed in brain regions involved in both homeostatic and hedonic feeding, and it circulates at reduced levels in patients with anorexia nervosa (AN). A single nucleotide polymorphism in the gene encoding for BDNF (Val66Met) has been associated with worse outcomes in patients with AN, and it is shown to promote anorectic behaviour in a mouse model of caloric restriction paired with social isolation stress. Previous animal models of the Val66Met polymorphism have been in mice because of the greater ease in modification of the mouse genome, however, the most widely-accepted animal model of AN, known as activity-based anorexia (ABA), is most commonly conducted in rats. Here, we examine ABA outcomes in a novel rat model of the BDNF Val66Met allelic variation (Val68Met), and we investigate the role of this polymorphism in feeding, food choice and sucrose preference, and energy expenditure. We demonstrate that the BDNF Val68Met polymorphism does not influence susceptibility to ABA or any aspect of feeding behaviour. The discrepancy between these results and previous reports in mice may relate to species–specific differences in stress reactivity.