Cocaine’s pleasurable and addictive effects are thought to be principally mediated via its blockage of dopamine transporters (DAT) which substantially increases the concentration of extracellular dopamine (DA), resulting in elevated stimulation of brain regions involved in reward and reinforcement behavior [16,24]. In line with this is evidence from human genetic, transgenic/knockout mouse, and inbred rodent studies that show that genetic differences in dopaminergic pathways mediate cocaine’s addictive or reinforcing properties [10]. The recent identification of a group of DA receptor-interacting proteins (DRIPs) [12,15,17] suggests that the intracellular activity of individual DA receptor subtypes is regulated by the concerted actions of signaling proteins [3] known as neuronal calcium sensors (NCS) [4] encoded by a set of 14 genes in humans [7]. NCS-1 is neuron specific [19] and exhibits an affinity for Ca2+ [8]. It inhibits receptor phosphorylation mediated by G protein-coupled receptor kinase 2 (GRK2) in a Ca2+-dependent manner [12]. Chronic cocaine exposure reduces the α-subunits of dopamine D2 receptor (D2R)-coupled Gi/o protein [21], Ca2+ influx {Hu, 2004 #155;Hu, 2004 #197} and activity of the adenylate cyclase calcineurin pathway in the
