Dopamine D1 receptor gene variation modulates opioid dependence risk by affecting transition to addiction.

ABSTRACT: Dopamine D1 receptor (DRD1) modulates opioid reinforcement, reward, and opioid-induced neuroadaptation. We propose that DRD1 polymorphism affects susceptibility to opioid dependence (OD), the efficiency of transition to OD, and opioid-induced pleasure response. We analyzed potential association between seven DRD1 polymorphisms with the following traits: duration of transition from the first use to dependence (DTFUD), subjective pleasure responses to opioid on first use and post-dependence use, and OD risk in 425 Chinese with OD and 514 healthy controls. DTFUD and level of pleasure responses were examined using a semi-structured interview. The DTFUD of opioid addicts ranged from 5 days to 11 years. Most addicts (64.0%) reported non-comfortable response upon first opioid use, while after dependence, most addicts (53.0%) felt strong opioid-induced pleasure. Survival analysis revealed a correlation of prolonged DTFUD with the minor allele-carrying genotypes of DRD1 rs4532 (hazard ratios (HR)?=?0.694; p?=?0.001) and rs686 (HR?=?0.681, p?=?0.0003). Binary logistic regression indicated that rs10063995 GT genotype (vs. GG+TT, OR?=?0.261) could predict decreased pleasure response to first-time use and the minor alleles of rs686 (OR?=?0.535) and rs4532 (OR?=?0.537) could predict decreased post-dependence pleasure. Moreover, rs686 minor allele was associated with a decreased risk for rapid transition from initial use to dependence (DTFUD?30 days; OR?=?0.603) or post-dependence euphoria (OR?=?0.603) relative to major allele. In conclusion, DRD1 rs686 minor allele decreases the OD risk by prolonging the transition to dependence and attenuating opioid-induced pleasure in Chinese.

SUBMITTER: Zhu F 

PROVIDER: S-EPMC3745389 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature