Hyperactivity in patients with anorexia nervosa and in semistarved rats: evidence for a pivotal role of hypoleptinemia

Patients with anorexia nervosa (AN) often show normal to elevated physical activity levels despite severe weight loss and emaciation. This is seemingly in contrast to the loss of energy and fatigue characteristic of other starvation states associated with weight loss. Despite the fact that historical accounts and clinical case studies of AN have regularly commented on the elevated activity levels, the behavior has become only recently the subject of systematic study. Because rodents and other species increase their activity upon food restriction leading to weight loss when given access to an activity wheel—a phenomenon referred to as activity-based anorexia or semi-starvation-induced hyperactivity (SIH)—it has been proposed that the hyperactivity in AN patients may reflect the mobilization of phylogenetically old pathways in individuals predisposed to AN. Exogeneous application of leptin in this animal model of AN has recently been shown to suppress completely the development of SIH. Hypoleptinemia, as a result of the food restriction, may represent the initial trigger for the increased activity levels in AN patients and in food-restricted rats. In the first and second parts of our review, we will summarize the relevant findings pertaining to hyperactivity in AN patients and in the rat model, respectively. We conclude with a synopsis and implications for future research.