Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABAA α2-subunit are associated with ethanol dependence in European American, white American, American plains Indian tribe and Russian populations [1], [2], [3], [4], though, unsurprisingly, this association is not evident in all populations [5], [6]. Although γ-aminobutyric acid A (GABAA) receptors have been suggested to represent a primary target for ethanol, the direct effects of ethanol at postsynaptic receptors are achieved only at high concentrations unlikely to be achieved by social drinkers (see [7] for review). Lower concentrations of ethanol can, however, can affect inhibitory GABAergic transmission by increasing release of GABA [8] and the release of neuromodulators which are active at the GABAA receptor, most notably neurosteroids [9].
