Native GABAA Receptors Get 'Drunk' But not their Recombinant Counterparts

Ethanol is arguably the most widely used (and abused) among psychoactive substances. The behavioral effects of ethanol consumption are well-acknowledged, as are its psychosocial consequences. Yet, relatively little is known about its mechanism of action in the central nervous system (CNS). At the systems level, it clearly targets a multitude of brain regions. At the cellular level, the prevailing thought is that ethanol exerts relatively specific modulatory effects on a number of neurotransmitter systems (e.g., γ-aminobutyric acid (GABA)ergic, glutamatergic, cholinergic, serotonergic), their corresponding receptors and/or intracellular second messenger intermediaries (for reviews see Deitrich et al., 1989; Grant and Lovinger, 1995; Morrow, 1995). These various effects of ethanol have modified the more traditional notion of a pleiotropic and non-specific action of ethanol on cellular membranes. With specific regard to the GABAA receptor, acute exposure to ethanol has been shown to exert potentiating effects. This has been implicated to account for sedation/motor incoordination at low ethanol concentrations and anesthetic consequences at higher concentrations.