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Differential alcohol modulation of GABAA and NMDA receptors

1999; Lippincott Williams & Wilkins; Volume: 10; Issue: 1 Linguagem: Inglês

10.1097/00001756-199901180-00019

1473-558X

Robert W. Peoples, Forrest F. Weight,

Neurotransmitter Receptor Influence on Behavior

NMDA and GABAA receptors are believed to be important CNS targets of alcohol action. In mouse hippocampal neurons, n-alcohols from ethanol to dodecanol enhanced GABA-activated ion current, whereas higher alcohols had no effect. Alcohols below pentanol affected NMDA receptors more potently than GABAA receptors. Increasing alcohol carbon chain length produced a greater average change in apparent binding energy and potency for modulation of GABAA than of NMDA receptor-channels, with the result that alcohols above pentanol affected GABAA receptors more potently than NMDA receptors. The anesthetic potency of n-alcohols in rats more closely reflected NMDA receptor modulatory potency for lower alcohols and GABAA receptor modulatory potency for higher alcohols. The results suggest that there may be fundamental differences in the sites through which alcohols affect NMDA and GABAA receptor function.