["European Eating Disorders Review, EarlyView. ", "\nABSTRACT\n\nObjective\nHyperactivity is a persistent and clinically relevant symptom in anorexia nervosa (AN). Hyperactivity is inversely correlated with leptin levels. While systemic leptin administration attenuates hyperactivity in rodent models, the specific brain regions mediating this effect remain unclear. Leptin acts on different brain areas involved in energy expenditure and motivation, including the ventral tegmental area (VTA), substantia nigra (SN) and lateral hypothalamus (LH). The present study aimed to determine through which of these regions leptin mediates its suppressive effects on hyperactivity, reflected in rodent models as compulsive running, in the Activity‐Based Anorexia (ABA) model.\n\n\nMethod\nTo identify the neural substrates of leptin's behavioural effects, female Wistar rats were stereotactically cannulated targeting the VTA, SN, or LH. Animals were subjected to the ABA paradigm, and site‐specific leptin (300 ng) or vehicle infusions were administered just before the onset of compulsive running. Running wheel activity (RWA), food intake, and body weight were assessed.\n\n\nResults\nPooled analyses identified the SN, LH, and VTA as functionally relevant nodes where leptin administration significantly reduced compulsive running. While leptin also attenuated the compensatory increase in food intake across all three regions, the robust suppression of running compared to the more modest effects on feeding suggests a partial functional dissociation within this distributed network.\n\n\nDiscussion\nThese findings indicate that leptin modulates compulsive running and feeding through a distributed neural network rather than a single discrete locus. The identification of the SN and LH as novel targets for the suppression of compulsive running provides a first mapping of the neural substrates underlying leptin's regulation of hyperactivity.\n\n"]