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The effect of switching pharmacological intervention during extinction on nicotine-evoked conditioned responding in rats

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Abstract

Rationale

Pharmacotherapies are often utilized to aid in smoking cessation, and switching medication when treating nicotine dependence has become more commonplace. Although common, little is known about the impact of the initial therapy on the effects of the subsequent therapy.

Objectives

To begin to fill this gap in our understanding, this project determined how switching compounds that share stimulus elements with nicotine during extinction altered extinction responding and generalization of this extinction back to nicotine.

Methods

Rats were trained in a discriminated goal-tracking task where nicotine administration was followed by intermittent sucrose access; sucrose was withheld following saline administration. In experiment 1, nornicotine supplanted nicotine in extinction sessions 1–3 and then a switch to varenicline on extinction sessions 4–6 was examined. In experiment 2, the reverse was investigated; varenicline to start extinction and then a switch to nornicotine. Generalization of extinction back to the nicotine stimulus was then assessed by generating a cumulative dose–effect curve.

Results

Generalization of extinction back to the training nicotine stimulus was greater if nornicotine had been received at any point in extinction compared to only receiving varenicline. Whereas, extinction with varenicline alone showed more generalization to lower doses of nicotine.

Conclusions

A switch in cessation pharmacotherapy during extinction did not impede or enhance generalization back to the nicotine-training stimulus. The nornicotine stimulus appears to share more stimulus overlap with the 0.4 mg/kg nicotine stimulus and varenicline may share more overlap with lower nicotine doses.

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This research was supported by NIH research grant DA034389. All Med-PC programs used in this research are available upon request to Rick A Bevins, Department of Psychology, University of Nebraska-Lincoln, Lincoln NE USA 68588-0308.

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Authors and Affiliations

  1. Department of Psychology, University of Nebraska-Lincoln, 238 Burnett Hall, Lincoln, NE, 68588-0308, USA

    Steven T. Pittenger, Lindsey C. Zeplin & Rick A. Bevins

  2. College of Pharmacy, University of Kentucky, 789 S. Limestone Street, Lexington, KY, 40536-0596, USA

    Linda P. Dwoskin

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  1. Steven T. Pittenger
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  2. Lindsey C. Zeplin
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  3. Linda P. Dwoskin
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  4. Rick A. Bevins
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Correspondence to Rick A. Bevins.

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Pittenger, S.T., Zeplin, L.C., Dwoskin, L.P. et al. The effect of switching pharmacological intervention during extinction on nicotine-evoked conditioned responding in rats. Psychopharmacology 232, 4347–4358 (2015). https://doi.org/10.1007/s00213-015-4067-y

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  • DOI: https://doi.org/10.1007/s00213-015-4067-y

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