The dopaminergic system is known to mediate drug reward and reinforcement. As the genetic risk for dependence on drugs of abuse, such as heroin and cocaine, has been shown to be substantial (Kendler et al., 2000, Kendler & Prescott, 1998, Tsuang et al., 1996, Tsuang et al., 1998), variants in genes of the dopamine system are potential candidates for drug dependence risk. The dopamine D2 receptor (DRD2) is coupled to inhibitory G proteins and its activation results in a decrease in intracellular cAMP (Strange, 1993). Human imaging studies have shown D2 receptor availability to be decreased in cocaine addicts, even after months of detoxification (Volkow et al., 1993). Striatal dopamine D2 and D3 receptor binding and dopamine release have also been found to be reduced in heroin dependent subjects when compared to healthy controls (Martinez et al., 2012). Furthermore, genetic association studies have found genetic variants in dopaminergic genes to be associated with cocaine dependence (Lohoff et al., 2010).
