A substantial body of evidence from preclinical studies has implicated GABAA receptors in the acute and chronic effects of ethanol including tolerance, dependence and withdrawal (reviewed in Enoch, 2008; Krystal et al, 2006). Rapid synaptic inhibition is mediated through GABAA receptors that are ligand-gated, chloride ion channels formed by pentameric complexes composed of subunits (α, β, γ, δ, ε, π, ρ), each of which have several isoforms (Barnard et al, 1998). Genes for the GABAA receptor subunit isoforms are clustered in several chromosomal regions. Expression of the various subunit isoforms varies across brain locations and during development. The mRNAs from the chromosome 4 cluster genes (GABRA2, GABRA4, GABRB1, GABRG1) predominate in rat embryo but these genes are generally down-regulated in the adult rat except in the hippocampus and in dopamine neurons in the substantia nigra and the ventral tegmental area (VTA) where they are highly expressed (Okada et al, 2004; Steiger and Russek, 2004; Wisden et al, 1992). This suggests that the chromosome 4 gene cluster may be implicated in addiction. Indeed, earlier genome-wide scans in American Indians and Caucasians
