The function of at least some GABAA-R subtypes in the brain recently has been identified using a combined molecular genetic and pharmacological approach (Rudolph & Möhler, 2004; Whiting, 2006). Thus, based on the evidence that most of the actions of diazepam are mediated via receptors composed of α1βγ2, α2βγ2, α3βγ2 and α5βγ2 subunits, a point mutation was introduced into the genes of the individual α subunits rendering the respective receptors insensitive to allosteric modulation by diazepam. A comparison of drug-induced behavioral responses in the mutated and wild-type mice then allowed the identification of diazepam effects that were missing or reduced in the mutant mice. Using this approach, it was demonstrated that α1βγ2 receptors mediate the sedative, anterograde amnestic and in part the anticonvulsant actions of diazepam (Rudolph et al., 1999; McKernan et al., 2000). The anxiolytic activity of diazepam is mediated primarily by GABAA-Rs composed of α2 βγ2 subunits (Low et al., 2000), and, under conditions of high receptor occupancy, also by α3 GABAA-Rs (Dias et al., 2005; Yee et al., 2005). The α2βγ2 receptors are also implicated in some
