Identifying novel phenotypes of vulnerability and resistance to activity-based anorexia in adolescent female rats.

Objective: Activity-based anorexia is a translational rodent model that results in severe weight loss, hyperactivity, and voluntary self-starvation. The goal of our investigation was to identify vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats.

Method: Sprague-Dawley rats were maintained under conditions of restricted access to food (N = 64; or unlimited access, N = 16) until experimental exit, predefined as a target weight loss of 30-35% or meeting predefined criteria for animal health. Nonlinear mixed effects statistical modeling was used to describe wheel running behavior, time to event analysis was used to assess experimental exit, and a regressive partitioning algorithm was used to classify phenotypes.

Results: Objective criteria were identified for distinguishing novel phenotypes of activity-based anorexia, including a vulnerable phenotype that conferred maximal hyperactivity, minimal food intake, and the shortest time to experimental exit, and a resistant phenotype that conferred minimal activity and the longest time to experimental exit.

Discussion: The identification of objective criteria for defining vulnerable and resistant phenotypes of activity-based anorexia in adolescent female rats provides an important framework for studying the neural mechanisms that promote vulnerability to or protection against the development of self-starvation and hyperactivity during adolescence. Ultimately, future studies using these novel phenotypes may provide important translational insights into the mechanisms that promote these maladaptive behaviors characteristic of anorexia nervosa.