ETHANOL, SEDATIVE HYPNOTICS, AND GLUTAMATE RECEPTOR FUNCTION IN BRAINAND CULTURED-CELLS

Ethanol, acutely, is a potent and selective inhibitor of the function of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor in pr imary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium liga nd binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chr onic consumption of ethanol by animals, the number of NMDA receptors ( measured by ligand binding) is increased in many brain areas. Similarl y, NMDA receptor function is increased in cerebellar granule cells exp osed chronically to ethanol. In the intact animal, this receptor up-re gulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In cont rast to ethanol, barbiturates have a greater inhibitory effect at the kainate subtype of glutamate receptor than at the NMDA receptor. After chronic barbiturate ingestion, kainate binding is decreased in certai n brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates o n NMDA and kainate receptor function is quite distinct from that of et hanol.