Candidate gene studies further support the association between dopamine and response to cocaine, by demonstrating specific variants located in dopaminergic genes that affect risk for cocaine dependence. The dopamine transporter gene solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 (SLC6A3, previously known as DAT or DAT1) has been the most frequently examined gene with respect to cocaine response. SLC6A3 knockout mice show reduced alteration of behavioral response (Giros et al., 1996) and brain glucose metabolism (Thanos et al., 2008) when exposed to cocaine. However, SLC6A3 knockout mice still self-administer cocaine (Rocha et al., 1998) and can still develop conditioned place preference in response to cocaine (Sora et al., 1998), demonstrating that SLC6A3 is not solely responsible for cocaine’s reinforcing effects.
