The Olsen and Spigelman groups have developed a chronic intermittent EtOH treatment paradigm in which rats are given a 5–6 g/kg dose of EtOH on alternate days for 60 treatments (120 days). This chronic administration of EtOH to rats on an intermittent regimen, for 60 repeated intoxicating doses and repeated withdrawal episodes, increases levels of α4 subunit mRNA in hippocampus with no significant change in the mRNAs for the α5 subunit (Mahmoudi et al. 1997). Similarly, rats that were exposed to intermittent episodes of intoxicating EtOH and withdrawal showed increased hippocampal α4 subunit peptide expression (Cagetti et al. 2003) and alteration in the pharmacological responses of GABAA receptors to benzodiazepine agonists and inverse agonists (Cagetti et al. 2003). The mRNA levels for the γ2S and γ1 subunits were also elevated. In CA1 pyramidal slices from chronic intermittent EtOH exposed rats, the baseline decay time of GABAAR-mediated mIPSCs was decreased, and the positive GABA receptor modulation of mIPSCs was also reduced compared with control rats. However, mIPSC potentiation by the α-preferring benzodiazepine ligand bretazenil was maintained, and mIPSC potentiation by Ro15-4513 was increased (Cagetti et al. 2003; Liang et al. 2009).
