There are several mechanisms by which a manipulation of GABAergic inhibition may affect responses to ethanol. Ethanol can activate postsynaptic receptors directly at high concentrations but whether this effect occurs at concentrations likely to be achieved socially is controversial [7]. Thus loss of GABAA α2-subunits is unlikely to change ethanol responses in the current experiments which result in relatively low blood alcohol concentrations, but currently cannot be ruled out as a possibility. These lower concentrations, however, can induce release of neurosteroids, which are known to act at GABAA receptors. The actions of neurosteroids have been shown to be only modestly influenced by the α-subunit composition of the receptor, with an alteration of the γ-subunit having the most effect [33]. Furthermore, changes in neurosteroid levels do not appear to alter the acute motor effects of ethanol [34], suggesting that a neurosteroid-dependent mechanism is unlikely to explain the acute differences observed in the current study. Increased GABA release also occurs in response to ethanol administration and is induced, at least in part, by a presynaptic GABAA receptor mechanism [35], [36]. The α2-subunit
