• Feng Zhu, Chun-xia Yan, Yi-chong Wen, Jiayin Wang, Jinbo Bi, Ya-ling Zhao, Lai Wei, Cheng-ge Gao, Wei Jia, and Sheng-bin Li.
• College of Medicine and Forensics, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China ; Key Laboratory of the Health Ministry for Forensic Sciences, Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China ; Key Laboratory of the Education Ministry for Environment and Genes Related to Diseases, Xi'an, Shaanxi, People's Republic of China.
• Plos One. 2013 Jan 1; 8 (8): e70805.

AbstractDopamine 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.

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