Substantial candidate gene research has also examined the dopamine receptor D1 gene (DRD1) for association with cocaine response. DRD1 knockout mice do not self-administer cocaine (Caine et al., 2007). DRD1-/- mice show decreased locomotion with cocaine exposure, compared to the increase in locomotion observed when DRD1 wild-type mice are exposed to cocaine (Xu et al., 1994). The relationship between dopamine receptors and cocaine response has also been demonstrated experimentally in humans. Evidence from agonist trials suggests that activation of D1-like (i.e., DRD1 and DRD5) receptors has opposite effects to those from activating D2-like (i.e., DRD2, DRD3 and DRD4) receptors, with D1-like agonists reducing cocaine-seeking behavior and D2-like agonists increasing this behavior (Self et al., 1996).
