Psychopharmacology

, Volume 188, Issue 3, pp 355–363

Association of OPRM1 A118G variant with the relative reinforcing value of nicotine

  • R. Ray
  • C. Jepson
  • F. Patterson
  • A. Strasser
  • M. Rukstalis
  • K. Perkins
  • K. G. Lynch
  • S. O’Malley
  • W. H. Berrettini
  • C. Lerman
Original Investigation

Abstract

Rationale

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.

Keywords

Nicotine Naltrexone OPRM1 Addiction Tobacco Genetic 

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • R. Ray
    • 1
    • 2
  • C. Jepson
    • 2
  • F. Patterson
    • 2
  • A. Strasser
    • 2
  • M. Rukstalis
    • 2
  • K. Perkins
    • 3
  • K. G. Lynch
    • 2
  • S. O’Malley
    • 4
  • W. H. Berrettini
    • 5
  • C. Lerman
    • 2
    • 6
  1. 1.Department of PharmacologyUniversity of PennsylvaniaPhiladelphiaUSA
  2. 2.Department of Psychiatry, Transdisciplinary Tobacco Use Research CenterUniversity of PennsylvaniaPhiladelphiaUSA
  3. 3.Department of PsychiatryUniversity of Pittsburgh School of MedicinePittsburghUSA
  4. 4.Department of PsychiatryYale University School of MedicineNew HavenUSA
  5. 5.Department of Psychiatry, Center for Neurobiology and BehaviorUniversity of PennsylvaniaPhiladelphiaUSA
  6. 6.Transdisciplinary Tobacco Use Research CenterUniversity of PennsylvaniaPhiladelphiaUSA

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