A complementary approach to the identification of genes contributing to the risk for human alcoholism is the analysis of alcohol-related phenotypes in animal models. For example, the alcohol-preferring (P) and -nonpreferring (NP) rats have been shown to be an animal model of alcohol dependence (Files et al., 1992; Li et al., 1991). The P rats voluntarily consume large amounts of alcohol for its pharmacological effects, work hard to obtain alcohol, and demonstrate tolerance when allowed to drink freely (Carr et al., 1998; Li et al., 1993; Murphy et al., 2002). Using data from this animal model, strong evidence of linkage for alcohol preference was found on rat chromosome 4, in a region which included several positional candidate genes including SNCA (Carr et al., 1998; Liang and Carr, 2006; Liang et al., 2003). Subsequent human studies have demonstrated that variation in SNCA does not contribute to the overall risk of alcohol dependence, but is associated with the phenotype of alcohol craving that may be related to the preference in rats (Bonsch et al., 2004; Bonsch et al., 2005a; Bonsch et al., 2005b; Bonsch et al., 2005c; Foroud et al., 2007;).
