Multiple SNPs in DRD3 were associated with craving alone, which supports the role of dopamine pathway genes in craving. Dopamine receptors in the striatum are down-regulated in alcohol dependent individuals (Volkow et al., 1996), and this reduction in striatal D2/3 receptors was shown to be associated with increased craving in alcoholics (Heinz et al., 2004). These authors subsequently demonstrated that the increased alcohol craving was inversely related to dopamine synthesis and binding in the same subjects (Heinz et al., 2005). Similarly, Tupala and colleagues reported reduced D2/D3 binding in the nucleus accumbens and amygdala among late-onset type 1 alcoholics, who have been hypothesized to have a deficit in dopamine availability (Tupala et al., 2001). A more general study revealed that decreased striatal D2/3 availability in healthy controls was associated with greater impulsivity and craving for stimulants (Buckholtz et al., 2010). D3 knock-out mice also show intense withdrawal from ethanol (Narita, Soma, Tamaki, Narita, & Suzuki, 2002). In fact dopamine activation has been proposed to treat addictions in general, (Blum, Liu, Shriner, & Gold, 2011) and more specifically, as a therapeutic
