Glucose regulates [3H](+)-amphetamine binding and Na+K+ ATPase activity in the hypothalamus: a proposed mechanism for the glucostatic control of feeding and satiety.

Binding sites for 3H-amphetamine in the hypothalamus may mediate the anorectic actions of amphetamine and related phenylethylamines. To investigate further the role of these sites in the central control of appetite, the binding of 3H-amphetamine to the hypothalamus and brainstem was measured following food deprivation and refeeding, the onset of genetic obesity, or the administration of 2-deoxy-D-glucose. Food deprivation for 24 to 72 hours reduced the Bmax for 3H-amphetamine binding in the hypothalamus and brainstem but not in other brain areas or peripheral tissues. The decrease in hypothalamic and brainstem 3H-amphetamine binding observed following food deprivation was time-dependent and rapidly reversed by brief refeeding with either rat chow or a 10% glucose solution. Moreover the changes in 3H-amphetamine binding were highly correlated to corresponding alterations in blood glucose concentration. Furthermore, D-glucose, but not L-glucose increases the number of hypothalamic 3H-amphetamine binding sites when administered in vivo or when added to hypothalamic slices in vitro. These data suggest that the 3H-amphetamine binding site in the hypothalamus and (or) brainstem may be coupled to a central "glucostat."