Development of, and recovery from, activity-based anorexia in female rats.

Activity-based anorexia occurs in rats maintained on a restricted-feeding schedule while given free access to running wheels. These conditions induce high levels of wheel running and rapid weight loss. Although this procedure was developed as an animal model of anorexia nervosa, it has been studied primarily in male rats. Our goal was to examine the development of, and recovery from, activity-based anorexia in female rats. Food intake, wheel running, body weight, and phase of the estrous cycle were monitored daily prior to, during, and after a period of restricted feeding in which access to food was limited to 2 h/day. Food intake, body weight, and estrous cyclicity were also monitored in a control group housed without access to running wheels. Prior to food restriction, rats with wheels displayed high levels of wheel running and consumed more food than rats without wheels. Despite that both groups consumed similar amounts of food during the restricted-feeding phase, only rats with wheels developed symptoms of activity-based anorexia, including increased wheel running, rapid weight loss, and disruptions in estrous cyclicity. Recovery from activity-based anorexia was associated with hypoactivity and hyperphagia. Resumption of estrous cycles occurred when the weight lost during food restriction was regained. Hyperphagia, but not hypoactivity, was maintained following resumption of estrous cycles; however, this hyperphagia was limited to nonestrous phases. Our findings suggest that recovery from activity-based anorexia is mediated primarily by an increase in orexigenic signaling that promotes pronounced hyperphagia, and that the increase in satiogenic signaling during estrus abolishes this compensatory hyperphagia.