Differential alcohol modulation of GABA_A and NMDA receptors

Abstract

NMDA and GABA_A 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 GABA_A receptors. Increasing alcohol carbon chain length produced a greater average change in apparent binding energy and potency for modulation of GABA_A than of NMDA receptor-channels, with the result that alcohols above pentanol affected GABA_A 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 GABA_A receptor modulatory potency for higher alcohols. The results suggest that there may be fundamental differences in the sites through which alcohols affect NMDA and GABA_A receptor function.