Alcohols stimulate gamma-aminobutyric acid receptor-mediated chloride uptake in brain vesicles: correlation with intoxication potency.

A series of short-chain alcohols, including ethanol, were examined for their abilities to stimulate gamma-aminobutyric acid (GABA) receptor-mediated chloride uptake into isolated brain vesicles. All of the alcohols tested stimulated 36 chloride uptake, at concentrations that occur during acute intoxication, and their potencies in stimulating GABA receptor-mediated chloride uptake were highly correlated with both their intoxication potencies in rats (r = 0.96; P less than 0.0001) and their membrane/buffer partition coefficients (r = 0.91; P less than 0.0005). Thus, the activity of alcohols at the GABA receptor-coupled chloride ion channel appears to be related to their ability to enter hydrophobic regions of the neuronal membrane. These data suggest that the anxiolytic, sedative/hypnotic and intoxicating properties of ethanol may, in part, be mediated via an action at central GABA receptors.