Recent work has suggested that alterations in GABAA receptor expression may underlie acquired ethanol tolerance. Studies indicate that a single high ethanol exposure results in alterations in GABAA receptor subunit expression. One hour following ethanol exposure, α4 and δ surface expression is decreased in the hippocampal CA1 region, but no difference in total subunit levels is found (Liang et al. 2007). This decrease in cell surface extrasynaptic receptors is associated with a decrease in ethanol-enhanced tonic current. Furthermore, a significant enhancement of surface expression of α4 and γ2 subunit proteins, as well as a decrease in α1 and δ subunits, was noted 2 days following ethanol exposure. Additionally, the ethanol-induced increase in α4 subunit expression requires the binding of heat shock factor 1 at a downstream site (Pignataro et al. 2007). These adaptive changes are accompanied by an increase in mIPSC response to ethanol and decreased response to diazepam (Liang et al. 2007), suggesting that the observed changes in receptor expression might underlie altered sensitivity to ethanol. Furthermore, chronic ethanol exposure altered the recovery of baseline spontaneous neural activity of
