Pharmacologic dissection of GABAA receptors in ethanol action has also identified a potential role for GABAA receptor subtypes in ethanol reinforcement. For instance, α1-GABAA receptors in the ventral pallidum are involved in the reinforcing properties of ethanol (Harvey et al. 2002). Systemic administration or infusion into the ventral pallidum of an α1 selective mixed benzodiazepine agonist–antagonist, 3-propoxy-β-carboline hydrochloride, reduces ethanol-maintained responding in ethanol-preferring rats. α1-GABAA receptors have also been implicated in ethanol-related heightened aggressive behavior (de Almeida et al. 2004). Administration of the benzodiazepine antagonist flumazenil or the preferential α1 antagonist, β-carboline-3-carboxylate-t-butyl ester, decreases ethanol-related aggression in mice trained to self-administer ethanol. The α5-GABAA receptors appear to play a role in the rewarding, motor-impairing, and sedative effects of ethanol in rats, since the selective inverse-agonist RY023 impacts these actions (Cook et al. 2005). Furthermore, interactions between ethanol and benzodiazepines increase spatial memory deficits in animals (Takiguchi et al. 2006) and humans (Simpson and Rush 2002) implicating γ2-GABAA receptors in spatial memory impairment. The development of more subtype specific/selective compounds will aid in further elucidating the role of specific GABAA receptor
