Tonic and phasic effects of corticosterone on food restriction-induced hyperactivity in rats

In the experimental rat model of anorexia nervosa the interactions between the hyperactivity of the hypothalamo-pituitary-adrenal (HPA) axis and increased physical activity associated with food restriction remain unidentified. In addition to their role in energy homeostasis, glucocorticoids have complex effects in the central nervous system, increasing the salience of activities such as wheel running. The objective of the present study was to analyze the role of corticosterone (cort) on wheel activity in food-restricted rats. Lewis rats were adrenalectomized and replaced with pellets containing increasing amounts of cort that caused different steady-state plasma concentrations from low to high HPA activity. They were given free access to a running wheel and were fed ad libitum or food-restricted. We also investigated the acute effect of cort injection mimicking the prefeeding cort peak on prefeeding wheel activity. Wheel running induced by food restriction was nearly non-existent in adrenalectomized food-restricted rats and increased in a dose-related manner with cort replacement. An acute stimulation of activity was also expressed during the preprandial peak of cort, suppressed by adrenalectomy and experimentally restored by acute cort injection. No such effects of cort were found in ad libitum fed rats. Our data demonstrate that food restriction-induced hyperactivity is critically and quantitatively dependent upon cort, not only on the mean basal levels of the hormone but also on the secretory peak that accompanies the burst of preprandial activity. The present results have special relevance for the pathophysiology of anorexia nervosa and other compulsive behaviors.