The role of GABAA receptors in mediating the effects of alcohol in the central nervous system

Ethanol is a chemically simple compound that produces many well-known effects in humans. The prevailing idea for many years was that ethanol and other alcohols exerted their effects on the central nervous system (CNS) by non-selectively disrupting the lipid bilayers of neurons. However, in recent years, there has been an accumulation of evidence pointing to the importance of ligand-gated ion channels (LGICs) in mediating the effects of ethanol. Of these LGICs, γ-aminobutyric acid type A (GABA A ) receptors appear to occupy a central role in mediating the effects of ethanol in the CNS. GABA is the primary inhibitory neurotransmitter in the mammalian CNS, and activation of GABA A receptors by GABA tends to decrease neuronal excitability. This article reviews several aspects of GABA A receptor and ethanol interactions, including the evidence for short- and long-term modulation of GABA A receptors by ethanol and evidence for a GABA A receptor-related genetic component of alcoholism.