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

PLoS One. 2013 Aug 16;8(8):e70805. doi: 10.1371/journal.pone.0070805. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age of Onset
  • Alleles
  • Behavior, Addictive / epidemiology
  • Behavior, Addictive / genetics*
  • Behavior, Addictive / psychology
  • Case-Control Studies
  • China / epidemiology
  • Female
  • Humans
  • Logistic Models
  • Male
  • Opioid-Related Disorders / epidemiology
  • Opioid-Related Disorders / genetics*
  • Opioid-Related Disorders / psychology
  • Polymorphism, Single Nucleotide*
  • Receptors, Dopamine D1 / genetics*
  • Risk
  • Surveys and Questionnaires
  • Time Factors

Substances

  • DRD1 protein, human
  • Receptors, Dopamine D1

Grants and funding

This work was supported by grants from the National Science Foundation of China (No. 81172903), the Fundamental Research Funds for the Central Universities (2010), the Scientific Research Foundation of Education Ministry and HR Ministry of China for the Returned Overseas Scholars for C-XY. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.