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The α4β2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats

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Abstract

Introduction

The α4β2 nicotinic acetylcholine receptor partial agonist varenicline has greater efficacy than other pharmacotherapeutic aids for smoking cessation. This presents an opportunity to evaluate the predictive validity of rat models of nicotine taking and relapse. The aim of this study was to evaluate the ability of varenicline to attenuate nicotine self-administration and relapse, as modelled by the reinstatement model of nicotine relapse in rats.

Materials and methods

Rats were trained to respond for intravenous nicotine under a fixed ratio schedule of reinforcement. The effects of varenicline (0.3–3.0 mg/kg s.c.) on both nicotine and food self-administration and reinstatement of nicotine seeking were evaluated.

Results and discussion

Varenicline dose-dependently reduced nicotine self-administration and attenuated both nicotine prime and combined nicotine prime plus nicotine-paired cue-induced reinstatement. Varenicline had no effect on cue-induced reinstatement in the absence of a nicotine prime nor did it induce reinstatement when given alone.

Conclusion

The effects of varenicline on nicotine-induced reinstatement of drug-seeking are consistent with the demonstrated clinical efficacy of varenicline for smoking cessation.

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Acknowledgements

We wish to thank H. West, J. Wickens, E. Lawrence and W. Attwell for surgical support, A. Broad and D. Roberts for assisting in performance of behavioural studies and K. Williams for comments on earlier versions of this manuscript. At the time the study was conducted, Eoin O’Connor was a Pfizer employee. This study was sponsored by Pfizer Inc.

Conflict of interest statement

The authors declare that, except for income received from my primary employer, no financial support or compensation has been received from any individual or corporate entity over the past 3 years for research or professional service, and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. School of Psychology, University of Sussex, Falmer, Brighton, BN1 9QG, UK

    Eoin C. O’Connor

  2. Global Safety Pharmacology, Drug Safety Research and Development, Pfizer Global Research and Development, Sandwich, CT13 9NJ, UK

    Dale Parker & Andy N. Mead

  3. Systems Neurobiology, Pfizer Global Research and Development, Groton, CT 06340, USA

    Hans Rollema

  4. Pfizer Ltd., IPC 388, Sandwich, Kent, CT13 9NJ, UK

    Andy N. Mead

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  1. Eoin C. O’Connor
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  2. Dale Parker
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Correspondence to Andy N. Mead.

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O’Connor, E.C., Parker, D., Rollema, H. et al. The α4β2 nicotinic acetylcholine-receptor partial agonist varenicline inhibits both nicotine self-administration following repeated dosing and reinstatement of nicotine seeking in rats. Psychopharmacology 208, 365–376 (2010). https://doi.org/10.1007/s00213-009-1739-5

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