Leptin suppresses semi-starvation induced hyperactivity in rats: implications for anorexia nervosa

Semi-starvation induced hyperactivity (SIH) occurs in rodents upon caloric restriction. We hypothesized that SIH is triggered by the decline in leptin secretion associated with food restriction, To test this hypothesis, rats, which had established a stable level of activity, were treated with leptin or vehicle via implanted minipumps concomitantly to initiation of food res triction for 7 days, In a second experiment treatment was initiated after S IH had already set in. In contrast to the vehicle-treated rats, which incre ased their baseline activity level by 300%, the development of SIH was supp ressed by leptin. Furthermore, leptin was able to stop SIH, after it had se t in. These results underscore the assumed major role of leptin in the adap tation to semi-starvation. Because SIH has been viewed as a model for anore xia nervosa, we also assessed subjective ratings of motor restlessness in 3 0 patients with this eating disorder in the emaciated state associated with hypoleptinemia and after increments in leptin secretion brought upon by th erapeutically induced weight gain, Hypoleptinemic patients ranked their mot or restlessness higher than upon attainment of their maximal leptin level d uring inpatient treatment. Thus, hypoleptinemia might also contribute to th e hyperactivity frequently associated with anorexia nervosa.