title: Association of OPRM1 A118G variant with the relative reinforcing value of nicotine.
abstract: BACKGROUND
  The endogenous opioid system has been implicated in substance abuse and response to pharmacotherapies for nicotine and alcohol addiction. We examined (1) the association of the functional OPRM1 A118G variant with the relative reinforcing value of nicotine and (2) the main and interacting effects of the mu-opioid receptor antagonist naltrexone on nicotine reinforcement.
  
  
  METHODS
  In a within-subject, double-blind human laboratory study, 30 smokers of each OPRM1 genotype (A/A vs. A/G or G/G) participated in two experimental sessions following 4 days of orally administered naltrexone 50 mg or placebo. Participants completed a validated assessment of the relative reinforcing value of nicotine. This cigarette choice paradigm assesses self-administration of 0.6 mg nicotine vs. 0.05 mg (denicotinized) cigarettes after a brief period of nicotine abstinence.
  
  
  RESULTS
  The relative reinforcing value of nicotine (number of nicotine cigarette puffs) was predicted by a significant OPRM1 by gender interaction. Among women, the low-activity G allele (A/G and G/G) was associated with a reduced reinforcing value of nicotine; among male smokers, there was no association with genotype. Smokers carrying a G allele were also significantly less likely to differentiate the nicotine vs. denicotinized cigarettes by subjective ratings of satisfaction and strength. No evidence for an effect of naltrexone on nicotine reinforcement was found in the overall sample or in the genotype or gender subgroups.
  
  
  CONCLUSIONS
  This study provides initial evidence for an association of the OPRM1 A118G variant with nicotine reinforcement in women.
authors.affiliation: Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: R
authors.initials: R
authors.lastname: Ray
authors.forename: C
authors.initials: C
authors.lastname: Jepson
authors.forename: F
authors.initials: F
authors.lastname: Patterson
authors.forename: A
authors.initials: A
authors.lastname: Strasser
authors.forename: M
authors.initials: M
authors.lastname: Rukstalis
authors.forename: K
authors.initials: K
authors.lastname: Perkins
authors.forename: K G
authors.initials: KG
authors.lastname: Lynch
authors.forename: S
authors.initials: S
authors.lastname: O'Malley
authors.forename: W H
authors.initials: WH
authors.lastname: Berrettini
authors.forename: C
authors.initials: C
authors.lastname: Lerman
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects; D000293:Adolescent; D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*; D012054:Reinforcement, Psychology; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000523:psychology; D016540:Smoking Cessation / Q000523:psychology; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000517:prevention & control / Q000523:psychology
chemical_list: D009292:Narcotic Antagonists; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D009538:Nicotine