It is established that genetic variation in the alpha-2 subunit of the GABAA receptor (GABRA2) is associated with risk for alcohol dependence (Covault et al., 2004; Edenberg et al., 2004; Fehr et al., 2006; Lappalainen et al., 2005; Soyka et al., 2008). While the primary function of GABAA receptors is to mediate the activity of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system, GABAA receptors also play a role in the chronic and acute effects of alcohol including motor incoordination, anxiolysis, motivation for excessive drinking and alcohol withdrawal (Buck, 1996; Davies, 2003; Grobin et al., 1998; Koob, 2004; Krystal et al., 2006). Recently, GABRA2 has also been shown to exert its influence on anxiety (Enoch et al., 2006) and several disinhibitory traits such as conduct disorder (Dick et al., 2006), illicit drug dependence (Agrawal et al., 2006; Drgon et al., 2006) as well as nicotine dependence (Agrawal et al., 2008).
