Activity-based Anorexia for Modeling Vulnerability and Resilience in Mice

Activity-based anorexia (ABA) is a widely used rodent model of anorexia nervosa. It involves combining limited access to food with unlimited access to a running wheel, leading to a paradoxical decrease in food intake, hyperactivity, and life-threatening weight loss. Although initially characterized in rats, ABA has been tested in mice with results that vary based on strain, sex, age, the amount of time food is available, and the number of days of food restriction. Here, we present our ABA protocol for modeling both vulnerability and resilience to diet and exercise in C57BL/6 female mice. While vulnerable mice exhibit the expected increase in running, reduction in food intake, and excessive weight loss, resilient mice exhibit an adaptive increase in food intake, decrease in total wheel running, and weight stabilization. In contrast to previous ABA studies in which resilience is defined by the relative rate of weight loss, our protocol leads to a resilient phenotype that more closely resembles the maintenance of a stable bodyweight exhibited by most humans who diet and exercise without developing anorexia nervosa. This protocol will be useful for future studies aimed at identifying the physiological and neural adaptations underlying both resilience and vulnerability to this eating disorder.