title: Subjective response to alcohol among alcohol-dependent individuals: effects of the μ-opioid receptor (OPRM1) gene and alcoholism severity.
abstract: BACKGROUND
  Subjective response to alcohol has been examined as a marker of alcoholism risk. The A118G single-nucleotide polymorphism (SNP) of the mu-opioid receptor (OPRM1) gene has been previously associated with subjective response to alcohol in heavy drinkers. This study seeks to extend the literature by examining the effect of OPRM1 genotype on responses to alcohol in a sample of alcohol-dependent individuals. A secondary aim of this study is to examine alcoholism severity as a predictor of subjective responses to alcohol.
  
  
  METHODS
  Nontreatment seeking problem drinkers (n = 295) were assessed in the laboratory for clinical dimensions of alcohol dependence. Following prospective genotyping, 43 alcohol-dependent individuals across the 2 genotype conditions (AA, n = 23 and AG/GG, n = 20) were randomized to 2 intravenous infusion sessions: 1 of alcohol (target breath alcohol concentration = 0.06 g/dl) and 1 of saline. Measures of subjective responses to alcohol were administered in both infusion sessions.
  
  
  RESULTS
  Alcohol-dependent G-allele carriers reported greater alcohol-induced stimulation, vigor, and positive mood, as compared to A-allele homozygotes. There was no genotype effect on alcohol-induced sedation or craving. There was a statistical trend-level severity × alcohol interaction such that individuals at higher levels of severity reported greater alcohol-induced tension reduction.
  
  
  CONCLUSIONS
  These results support the hypothesis that OPRM1 genotype moderates the hedonic effects of alcohol, but not the sedative and unpleasant effects of alcohol, in a sample of alcohol-dependent patients. Results are discussed in light of a clinical neuroscience framework to alcoholism.
authors.affiliation: Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095-1563, USA. lararay@psych.ucla.edu
authors.forename: Lara A
authors.initials: LA
authors.lastname: Ray
authors.forename: Spencer
authors.initials: S
authors.lastname: Bujarski
authors.forename: James
authors.initials: J
authors.lastname: MacKillop
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Courtney
authors.forename: Peter M
authors.initials: PM
authors.lastname: Monti
authors.forename: Karen
authors.initials: K
authors.lastname: Miotto
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects* / Q000502:physiology; D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology; D000437:Alcoholism / Q000235:genetics* / Q000523:psychology*; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D000431:Ethanol