Abstract
Ethanol, acutely, is a potent and selective inhibitor of the function of theN-methyl-d-aspartate (NMDA) subtype of glutamate receptor in primary cultures of cerebellar granule cells. The effect of ethanol can be reversed by high concentrations of glycine, and nonequilibrium ligand binding studies in brain membrane preparations suggest that ethanol may act by decreasing the frequency of ion channel opening. After chronic consumption of ethanol by animals, the number of NMDA receptors (measured by ligand binding) is increased in many brain areas. Similarly, NMDA receptor function is increased in cerebellar granule cells exposed chronically to ethanol. In the intact animal, this receptor up-regulation may be associated with ethanol withdrawal seizures, which are attenuated by uncompetitive antagonists at the NMDA receptor. In contrast 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 isdecreased in certain brain areas, while ligand binding to the NMDA receptor is increased. Overall, the pattern of brain area-specific effects of barbiturates on NMDA and kainate receptor function is quite distinct from that of ethanol.
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This manuscript was submitted to the Proceedings of the Sixth Congress of the International Society for Biomedical Research on Alcoholism and to the Proceedings of the Symposium on Genetics and Alcoholism which was part of the Twenty-fifth Anniversary celebration of the Institute for Behavioral Genetics.
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Tabakoff, B., Hoffman, P.L. Ethanol, sedative hypnotics, and glutamate receptor function in brain and cultured cells. Behav Genet 23, 231–236 (1993). https://doi.org/10.1007/BF01067428
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DOI: https://doi.org/10.1007/BF01067428