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Translating the smoking cessation properties of the antidepressant nortriptyline using reinforcing, discriminative and aversive stimulus effects of nicotine in rats

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Abstract

Rationale

The antidepressant nortriptyline is a second-line pharmacotherapy for smoking cessation. Given that there is limited preclinical data available on the effects of nortriptyline on responses to nicotine, the present study sought to evaluate its effects on the reinforcing, discriminative stimulus (DS) and aversive effects of nicotine in male hooded Lister rats.

Methods

The effects of nortriptyline (0, 1, 3 and 10 mg/kg, i.p.) on responding under the control of a second order schedule of nicotine (0.03 mg/kg per infusion) intravenous self-administration (IVSA; n = 7), food-maintained responding (n = 6), discrimination of nicotine (0.2 mg/kg, s.c.) from saline in a two-lever procedure controlled by a fixed ratio and variable interval schedule of food reinforcement (n = 12) and on the development of nicotine- and lithium-induced conditioned taste aversions (CTA) (n = 8 per dose of nortriptyline) were examined.

Results

Nortriptyline (3 mg/kg) reduced responding for nicotine in the drug-free interval in which behaviour was supported by nicotine-associated cues and subsequent intervals in which nicotine was available; however, food-maintained responding was also reduced at the same dose. Nortriptyline (3 mg/kg) blocked the development of a nicotine-induced CTA but not a lithium-induced CTA, indicating that these effects are unlikely to be due to non-specific effects of nortriptyline on taste perception or learning. Lastly, nortriptyline had no effect on the DS properties of nicotine.

Conclusions

Nortriptyline appears to attenuate the reinforcing and aversive stimulus properties of nicotine, which may mediate its anti-smoking effects. However, the results should be interpreted with caution, as non-specific effects of nortriptyline may have contributed to these findings.

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Acknowledgements

This research was supported by Newcastle University, UK. We thank Parisa Rahimpourojani for her assistance with the conditioned taste aversion and discrimination experiments, and Emma Malcolm for her assistance with the nicotine self-administration experiment.

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Authors and Affiliations

  1. Psychobiology Research Laboratories, Institute of Neuroscience, Newcastle University, Newcastle Upon Tyne, UK

    Victoria C. Wing & Mohammed Shoaib

  2. Centre for Addiction and Mental Health, 33 Russell St., Toronto, ON, M5S 2S1, Canada

    Victoria C. Wing

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  1. Victoria C. Wing
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  2. Mohammed Shoaib
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Correspondence to Victoria C. Wing.

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Wing, V.C., Shoaib, M. Translating the smoking cessation properties of the antidepressant nortriptyline using reinforcing, discriminative and aversive stimulus effects of nicotine in rats. Psychopharmacology 219, 847–857 (2012). https://doi.org/10.1007/s00213-011-2413-2

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  • DOI: https://doi.org/10.1007/s00213-011-2413-2

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