Abstract: | The inhibitory potency of ethanol upon excitatory amino acid induced depolarizations of rat hippocampal CA1 pyramidal cells was assessed in the presence and absence of magnesium (Mg2+) using the grease-gap technique. Ethanol shifted theN-methyl-d-aspartate (NMDA) dose-response curves to the right in a non-parallel manner. In the presence of Mg2+, ethanol appeared to be a more effective NMDA antagonist (IC50 47 mM) than in the absence of Mg2+ (IC50 107 mM). The IC50 for ethanol upon non-NMDA mediated CA1 pyramidal cell depolarizations was in excess of 170 mM. These results strongly suggest a preferential inhibitory action of ethanol against NMDA, rather than non-NMDA, mediated responses. Experiments in which ethanol and Mg2+ were covaried indicated that these substances act by two distinct mechanisms to antagonize the action of NMDA. These effects of ethanol, at concentrations which elicit intoxication(< 50mM) but not anesthesia, suggest that the NMDA receptor complex may play an important role in the acute effects of ethanol. |