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

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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.

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Acknowledgements

The authors would like to acknowledge the contributions of John Dahl, Stephanie Restine, and Hetty Rodriguez for genotyping; Susan Ware and Angela Pinto for assistance with data management; Dr. Kenneth Rockwell for assistance with medication dispensing; and Maryanne Foster for assistance with manuscript preparation. We also would like to thank Rebecca Ashare, Elizabeth Cherry, Sean Fleming, Korlei Mensah, Paul Sanborn, and Kia Wilson for assistance with data collection.

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Authors and Affiliations

  1. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    R. Ray

  2. Department of Psychiatry, Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, Philadelphia, PA, 19104, USA

    R. Ray, C. Jepson, F. Patterson, A. Strasser, M. Rukstalis, K. G. Lynch & C. Lerman

  3. Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA

    K. Perkins

  4. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06519, USA

    S. O’Malley

  5. Department of Psychiatry, Center for Neurobiology and Behavior, University of Pennsylvania, Philadelphia, PA, 19104, USA

    W. H. Berrettini

  6. Transdisciplinary Tobacco Use Research Center, University of Pennsylvania, 3535 Market Street, Suite 4100, Philadelphia, PA, 19104, USA

    C. Lerman

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  1. R. Ray
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  2. C. Jepson
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  9. W. H. Berrettini
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  10. C. Lerman
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Corresponding author

Correspondence to C. Lerman.

Additional information

This research was supported by grants from the National Institute on Drug Abuse (RO1 DA017555-03) and National Cancer Institute (P50 CA/DA84718) (C.L.) and funding from the Commonwealth of Pennsylvania.

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Ray, R., Jepson, C., Patterson, F. et al. Association of OPRM1 A118G variant with the relative reinforcing value of nicotine. Psychopharmacology 188, 355–363 (2006). https://doi.org/10.1007/s00213-006-0504-2

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  • DOI: https://doi.org/10.1007/s00213-006-0504-2

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