The dopaminergic brain system is important for drug reward [11], thus making genes involved in these circuits plausible candidates for influencing susceptibility to substance use disorders. In fact, several genes coding for the dopaminergic system have been investigated in CA including genes for the dopamine receptor D2 (DRD2) [20], D3 [6], D4 [1] the (DAT) [22] and the catechol-O-methyl-transferase (COMT) gene [18]. The results of all these studies have been conflicting with some positive reports and some negative findings, possibly due to small sample sizes and the complex genetic nature of CA. In this study, we focused on dopamine receptor-interacting proteins, since they represent a novel target in the investigation of the genetics of CA. Genetic variation in the NCS-1 gene may alter NCS-1 protein levels and/or function and thus have an effect on the rate of D2 receptor desensitization and internalization, consistent with data in human abstinent cocaine abusers that show decreased D2 receptor availability in the striatum [28]. To our knowledge, this is the first study investigating NCS-1 as a risk gene for CA. Earlier, Dahl et al.
