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Chunk #12 — Genome-Wide Linkage Studies — Alcohol Use Disorders and GABRA2

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Identifying genetic variation for alcohol dependence.
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yes

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Animal models also have begun to address these functional aspects of GABRA2, as follows: Work with frog eggs (i.e., Xenopus oocytes) has demonstrated that the α2 subunits are involved in regulating GABA currents upon ethanol exposure (Hurley et al. 2009).Studies of mice that had been genetically modified to produce or not produce the GABA-α2 subunit (i.e., knock-in and knock-out mice) demonstrated the important role of this subunit in anxiolysis (Boehm et al. 2004; Dixon et al. 2008). Additional studies with these animals provided evidence for the involvement of the α2 subunits in the hypnotic effects of ethanol when administered together with the benzodiazepine diazepam (Tauber et al. 2003).In analyses comparing alcohol-preferring (P) and non-preferring (NP) rats (McBride and Li 1998), Liu and colleagues (2011) reported that P rats show elevated levels of GABA-A subunits, including the α2 subunits, in a brain region called the central nucleus of the amygdala. Intriguingly, when molecules that specifically could inhibit the GABRA2 gene (i.e., α2 silent RNA [siRNA]) were introduced into the central amygdala, even the P animals no longer demonstrated binge drinking for