Effects of corticosteroid synthesis inhibitors on the sensitization of reward by food restriction.

Abstract Chronic food restriction sensitizes animals to the rewarding effects of food, drugs and lateral hypothalamic electrical stimulation. The present study employed a curve-shift analysis of lateral hypothalamic self-stimulation (LHSS) to evaluate whether the elevated plasma corticosterone levels that accompany food restriction mediate the sensitization of reward. In Experiment 1, two adrenocorticoid synthesis inhibitors, aminoglutethimide and metyrapone, were administered to food-restricted rats and the magnitude of plasma corticosterone suppression was determined at two post-administration time points. In Experiment 2, these compounds were administered to ad libitum fed and food-restricted rats whose LHSS behavior was evaluated at a time coincident with suppression of corticosterone. It was found that neither compound reversed the sensitizing effect of food-restriction on the rewarding efficacy of brain stimulation. However, aminoglutethimide (50 mg/kg) produced an increase in maximal response rates (a performance factor) across groups while metyrapone (100 mg/kg) produced a decrease. The most interesting result of this study was that 2 h after aminoglutethimide administration, when corticosterone levels had recovered from suppression, the rewarding efficacy of LHSS increased markedly in food-restricted rats. Possible explanations for this effect, including adrenocortical rebound, alterations in neurosteroid synthesis, and exacerbation of metabolic need are discussed.