shown by reduced ethanol-induced loss of righting reflex in α2- GABAA receptor knockout animals (Boehm et al. 2004b). Studies using benzodiazepine-insensitive histidine101 to arginine (H101R) knockin mice have also indicated a role for α2-GABAA receptors in ethanol’s sedative-hypnotic effects. The combined effect of subthreshold doses of diazepam and ethanol resulted in a loss of righting reflex in α1-, α3-, and α5-, but not α2- (H101R) GABAA receptor knockin mice (Tauber et al. 2003). Additionally, β2-GABAA receptors may also play a role in ethanol’s sedative-hypnotic effects, as male β2-GABAA receptor knockout mice displayed reduced loss of righting reflex duration compared to controls (Blednov et al. 2003a). Surprisingly, given the similarity of benzodiazepine and ethanol effects on anxiety, the α1-, α2-, α4-, α5-, γ2L-, and δ-GABAA receptor knockout mice did not display changes in ethanol-induced anxiolysis (Boehm et al. 2004b; Chandra et al. 2008; Homanics et al. 1999a; Kralic et al. 2003; Mihalek et al. 2001). Further studies are clearly needed to elucidate whether specific GABAergic receptor subtypes mediate the anxiolytic effects of ethanol.
