Magnesium-dependent inhibition of N-methyl-D-aspartate receptor-mediated synaptic transmission by ethanol.

Previous studies have indicated that ethanol (EtOH) has a relatively specific effect on excitatory synaptic transmission by inhibiting function of the N-methyl-D-aspartate receptor. We have found that EtOH potently inhibits N-methyl-D-aspartate-mediated synaptic currents in the basolateral amygdala, a brain region associated with actions of anxiolytic agents such as EtOH. This inhibitory effect of EtOH requires the presence of magnesium (Mg++). The dependence of the effect of EtOH on the presence of Mg++ suggests a possible molecular site of the action of EtOH in the vicinity of Mg++ binding sites on the N-methyl-D-aspartate receptor-channel complex. Because EtOH consumption may result in reductions in free brain Mg++, this dynamic interaction between EtOH and Mg++ may have important implications for understanding the behavioral effects of EtOH.