Ethanol inhibition of NMDA mediated depolarizations is increased in the presence of Mg2+.

Article date: 1991/4/19

PubMed ID: 2070260

Journal name: Brain research (ISSN: 0006-8993)


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 the N-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 (less than 50 mM) but not anesthesia, suggest that the NMDA receptor complex may play an important role in the acute effects of ethanol.

Author List: Martin D, Morrisett R A, Bian X P, Wilson W A, Swartzwelder H S

Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Neuromuscular Depolarizing Agents; Ibotenic Acid; Ethanol; N-Methylaspartate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Magnesium; Kainic Acid; Glycine;

Mesh terms: Animals; Electrophysiology; Ethanol/pharmacology; Female; Glycine/metabolism; Hippocampus/drug effects; Ibotenic Acid/analogs & derivatives; In Vitro Techniques; Kainic Acid/pharmacology; Magnesium/pharmacology; N-Methylaspartate/antagonists & inhibitors; Neuromuscular Depolarizing Agents; Rats; Rats, Inbred Strains; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;

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