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Differentiating the primary reinforcing and reinforcement-enhancing effects of varenicline

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Abstract

Rationale

Varenicline (VAR), a smoking cessation aid that is a partial agonist at nicotinic receptors, mimics the reinforcement-enhancing effects of nicotine. Varenicline, when accompanied by non-drug cues, is self-administered by rats, though it is unclear whether this results from varenicline acting as a primary reinforcer or a reinforcement enhancer of the cues.

Objectives

This study sought to disentangle these two potential actions.

Methods

Rats were allowed to self-administer intravenous nicotine, saline, or varenicline during 1-h sessions in operant chambers equipped with two levers. Five groups had concurrent access to drug infusions and a moderately reinforcing visual stimulus (VS) for responding on separate levers. Meeting the reinforcement schedule on one lever was reinforced with VAR (0.01, 0.06, 0.1 mg/kg/infusion), nicotine (0.06 mg/kg/infusion), or saline, while meeting the same schedule on the other lever delivered the VS. Additional groups were reinforced for pressing a single “active” lever and received VAR paired with the VS, the VS with response-independent infusions of VAR, or VAR alone (0.1 mg/kg/infusion).

Results

Rats readily responded for VAR paired with VS on a single lever. However, when VAR was the only reinforcer contingent on a response, rats did not respond more than for saline.

Conclusions

These findings show that VAR does not serve as a primary reinforcer in rats at doses that increase responding for non-drug reinforcers. These data are consistent with research showing that the primary reinforcing effects of VAR are weak, at best, and that the primary reinforcing and reinforcement-enhancing actions of nicotinic drugs are pharmacologically distinct.

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Acknowledgments

This work was supported by the National Institutes of Health grants DA-10464 and DA-24801. Varenicline was generously donated by Pfizer, Inc.

Conflict of interest

The authors have no conflicts of interest to disclose.

Author information

Authors and Affiliations

  1. Department of Neuroscience, University of Pittsburgh, A210 Langley Hall, 5th and Ruskin Avenue, Pittsburgh, PA, 15260, USA

    Rachel L. Schassburger & Alan F. Sved

  2. Department of Psychology, University of Pittsburgh, 210 S. Bouquet Street, Pittsburgh, PA, 15260, USA

    Melissa E. Levin, Anthony R. Caggiula, Eric C. Donny & Alan F. Sved

  3. Department of Psychology, Mercyhurst University, 103 Briggs Hall, Erie, PA, 16546, USA

    Matthew T. Weaver

  4. Department of Psychology, East Tennessee State University, PO Box 70649, Johnson City, TN, 37614, USA

    Matthew I. Palmatier

Authors
  1. Rachel L. Schassburger
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  2. Melissa E. Levin
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  3. Matthew T. Weaver
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  4. Matthew I. Palmatier
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  5. Anthony R. Caggiula
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  6. Eric C. Donny
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  7. Alan F. Sved
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Corresponding author

Correspondence to Alan F. Sved.

Additional information

Eric C. Donny and Alan F. Sved contributed equally.

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Schassburger, R.L., Levin, M.E., Weaver, M.T. et al. Differentiating the primary reinforcing and reinforcement-enhancing effects of varenicline. Psychopharmacology 232, 975–983 (2015). https://doi.org/10.1007/s00213-014-3732-x

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  • DOI: https://doi.org/10.1007/s00213-014-3732-x

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