brain regions except the thalamus, dentate gyrus, and striatum (Bencsits et al. 1999; Chandra et al. 2006; Pirker et al. 2000). However, selective modulation of α4 subunit expression in the hippocampus, using antisense oligonucleotides, has been shown to significantly alter the functional properties of GABAA receptors and modulate steroid withdrawal excitability (Moran et al. 1998; Smith et al. 1998). Therefore, despite the relatively low expression of α4 subunit peptide, modulation of α4 subunit expression clearly influences GABAA receptor function and GABA-mediated behaviors in vivo. Recombinant expression and homologous gene deletion studies have shown that functional properties are regulated by the subunit composition of GABAA receptors. For example, recombinant GABAA receptors with α4β2γ2 subunits respond to GABA and benzodiazepine agonists with lower efficacy than α1β2γ2 receptors (Whittemore et al. 1996). Moreover, homologous genetic deletion of α1 subunits dramatically alters the pharmacological properties of GABAA receptors, reducing the potency and efficacy of GABA and of the benzodiazepine diazepam (Kralic et al. 2002a, b). Hence, alterations in GABAA receptor subunit expression appear critically important in regulation of GABAA receptor function following chronic ethanol administration.
