Interaction of ethanol with the GABAA receptor in the rat brain: possible involvement of endogenous steroids.

The effect of ethanol on the binding of gamma-aminobutyric acid (GABA) agonist, [3H]muscimol, to crude synaptosomal membranes prepared from various rat brain regions was investigated, in vitro, at 37 degrees C. Ethanol altered specific muscimol binding in a biphasic manner--reducing it at concentrations less than 10 mM and subsequently increasing specific binding at concentrations greater than 10 mM. The former effect was due to a decrease of the receptor affinity for an agonist, and the latter, due to an increase of the receptor density. Ethanol interfered also with the effects of "GABAergic" modulatory steroids on muscimol binding. This suggests that steroid-ethanol interactions, occurring at the level of the plasma membrane, may be involved in the molecular mechanism of action of ethanol on the GABAA receptor.