Glucostatic regulation of hypothalamic and brainstem [3H](+)-amphetamine binding during food deprivation and refeeding.

Abstract

Saturable and stereospecific binding sites for [3H](+)-amphetamine have been identified in rat hypothalamus and structure-activity studies suggest that these sites may mediate the anorectic actions of amphetamine and related phenylethylamines. In order to determine whether these binding sites may be involved in the physiological control of appetite, [3H](+)-amphetamine binding was measured in crude synaptosomal membranes prepared from various brain regions following food deprivation and refeeding. Rats deprived of food for 24 to 72 h exhibited time-dependent reductions in body weight, blood glucose concentration, and specific [3H](+)-amphetamine binding in hypothalamus and brainstem. No change in specific [3H](+)-amphetamine binding was found in the frontal cortex, striatum, cerebellum, or liver prepared from these same animals. The decrease in specific [3H](+)-amphetamine binding in both the hypothalamus and brain stem following food deprivation was rapidly and completely reversed by allowing animals brief access to food or a 10% glucose solution. The changes in [3H](+)-amphetamine binding in hypothalami and brainstem of food-deprived and refed rats were also highly correlated with blood glucose concentration. Further, parenteral administration of D-glucose, but not L-glucose, to either fed or food-deprived rats significantly increased the number of [3H](+)-amphetamine binding sites in hypothalamus. These data suggest that the [3H](+)-amphetamine binding site in the hypothalamus and (or) brainstem may function in the 'glucostatic' regulation of appetite.