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Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration

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Abstract

Rationale

Much evidence indicates that individuals use tobacco primarily to experience the psychopharmacological properties of nicotine. Varenicline, a partial α4β2 nicotinic acetylcholine receptor (nAChR) agonist, is effective in reducing nicotine craving and relapse in smokers, suggesting that α4β2 nAChRs may play a key role in nicotine dependence. In rats, the effect of varenicline on nicotine intake has only been studied with limited access to the drug, a model of the positive reinforcing effect of nicotine. Varenicline has not been tested on the increase in motivation to take nicotine in nicotine-dependent rats.

Objectives

The present study evaluated the effects of varenicline on nicotine intake in rats with extended access to nicotine self-administration (23 h/day), a condition leading to the development of nicotine dependence. We hypothesized that varenicline’s effects on nicotine self-administration would be greater in rats with extended than limited access to the drug and after forced abstinence rather than during baseline self-administration.

Results

Varenicline dose-dependently decreased nicotine self-administration in rats with limited (1 h/day) and extended (23 h/day) access. Despite an increased sensitivity to the motivational effects of abstinence on nicotine intake compared with limited-access rats, varenicline was equally effective in decreasing nicotine intake in dependent rats with extended access to nicotine.

Conclusion

These results suggest that α4β2 nAChRs are critical in mediating the positive reinforcing effects of nicotine but may not be a key element underlying the negative reinforcement process responsible for the increased nicotine intake after abstinence in dependent subjects.

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Acknowledgments

This is publication number 20551 from The Scripps Research Institute. This work was supported by the Tobacco-Related Disease Research Program (TRDRP) from the State of California (grant 17RT-0095), the Pearson Center for Alcoholism and Addiction Research, and the National Institute on Drug Abuse (DA12001 and DA023597)). The authors thank Robert Lintz, Shayla Vu, Yanabel Grant, and Molly Brennan for their technical assistance and Taryn Grieder for helpful discussions. We also thank Michael Arends for his editorial assistance.

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Authors and Affiliations

  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA

    Olivier George, Allison Lloyd & George F. Koob

  2. Research Triangle Institute, Organic and Medicinal Chemistry, Research Triangle Park, NC, 27709, USA

    F. Ivy Carroll

  3. Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, 23298, USA

    M. Imad Damaj

Authors
  1. Olivier George
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  2. Allison Lloyd
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  3. F. Ivy Carroll
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  4. M. Imad Damaj
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  5. George F. Koob
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Correspondence to Olivier George.

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George, O., Lloyd, A., Carroll, F.I. et al. Varenicline blocks nicotine intake in rats with extended access to nicotine self-administration. Psychopharmacology 213, 715–722 (2011). https://doi.org/10.1007/s00213-010-2024-3

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  • DOI: https://doi.org/10.1007/s00213-010-2024-3

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