EFFECTS OF CORTICOSTEROID SYNTHESIS INHIBITORS ON THE SENSITIZATION OF REWARD BY FOOD RESTRICTION

Chronic food restriction sensitizes animals to the rewarding effects o f food, drugs and lateral hypothalamic electrical stimulation. The pre sent study employed a curve-shift analysis of lateral hypothalamic sel f-stimulation (LHSS) to evaluate whether the elevated plasma corticost erone levels that accompany food restriction mediate the sensitization of reward. In Experiment 1, two adrenocorticoid synthesis inhibitors, aminoglutethimide and metyrapone, were administered to food-restricte d rats and the magnitude of plasma corticosterone suppression was dete rmined 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 suppressi on of corticosterone. It was found that neither compound reversed the sensitizing effect of food-restriction on the rewarding efficacy of br ain stimulation. However, aminoglutethimide (50 mg/kg) produced an inc rease in maximal response rates (a performance factor) across groups w hile metyrapone (100 mg/kg) produced a decrease. The most interesting result of this study was that 2 h after aminoglutethimide administrati on, when corticosterone levels had recovered from suppression, the rew arding efficacy of LHSS increased markedly in food-restricted rats. Po ssible explanations for this effect, including adrenocortical rebound, alterations in neurosteroid synthesis, and exacerbation of metabolic need are discussed.