Huang et al.62 implicated DRD3 as a susceptibility gene for ND, but this result has not yet been replicated. Meanwhile, Stapleton et al.63 showed a significant association of a dopamine transporter gene (SLC6A3) with smoking cessation in a meta-analysis of 2,155 subjects (80% of European ancestry), although this finding received only weak support from another study on age at smoking initiation in 668 Asians.64 This gene group includes two others, protein phosphatase 1 regulatory subunit 1B (PPP1R1B) and μ-opioid receptor (OPRM1), on the basis of their functional connections with dopamine in studies of other addictive substances. PPP1R1B, also known as dopamine- and cAMP-regulated neuronal phosphatase (DARPP-32), encodes a key phosphoprotein involved in the regulation of several signaling cascades for dopaminoceptive neurons in several areas of the brain, which also is required for the biochemical effects of cocaine.65 Activation of OPRM1 in the ventral tegmental area suppresses the activity of inhibitory GABAergic interneurons, resulting in disinhibition of dopamine neurons and dopamine release from terminals in the ventral striatum.66 OPRM1 A118G variation is a genetic determinant of the striatal dopamine response to
