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Effect of bupropion on nicotine self-administration in rats

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Abstract

Rationale and objective

The mechanisms underlying the therapeutic efficacy of bupropion as a smoking cessation agent are unknown. Bupropion inhibits monoamine uptake as well as neuronal nicotinic receptor (nAChR) function. The present study compared effects of bupropion on nicotine self-administration to those of other stimulant drugs (methamphetamine and apomorphine) that lack nAChR activity in order to determine its mechanism of action. To determine the specificity of bupropion-induced changes in nicotine self-administration, the ability of bupropion to alter sucrose-maintained responding or amphetamine self-administration was determined.

Methods

In nicotine and amphetamine self-administration and sucrose-maintained responding experiments, rats responded for nicotine (0.01 or 0.02 mg/kg per infusion, IV), amphetamine (0.2 mg/kg per infusion, IV) and sucrose pellets (45 mg), respectively, on a fixed ratio 5 schedule. Once responding stabilized, rats were pretreated 15 min before the session with bupropion (1–78 mg/kg) or vehicle. The ability of methamphetamine (0.3–3 mg/kg) or apomorphine (0.01–0.2 mg/kg) to alter responding for nicotine (0.02 mg/kg per infusion, IV) was determined.

Results

Bupropion produced a biphasic dose-response pattern at both nicotine infusion doses, increasing infusions at low bupropion doses and decreasing infusions at high bupropion doses. Methamphetamine produced a similar biphasic pattern, whereas apomorphine only decreased nicotine infusions at high doses. Bupropion dose-dependently decreased responding for sucrose and amphetamine.

Conclusions

These results suggest that high bupropion doses decrease responding nonspecifically; whereas low bupropion doses selectively increase responding for nicotine. The increase in nicotine self-administration is likely due to inhibition of dopamine and norepinephrine transporters, combined with inhibition of nAChRs.

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Acknowledgements

This research was supported by the Pharmacia Corporation (Kalamazoo, Mich., USA). A.S. Rauhut was supported by a National Institutes of Health, National Research Service Award (T32 DA07304) from the National Institute on Drug Abuse. The authors wish to thank Laura Fenton, Thomas Green and Brenna Shortridge for their excellent technical assistance.

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Author notes

  1. Anthony S. Rauhut

    Present address: Department of Psychology, Dickinson College, PO Box 1773, Carlisle, PA 17013, USA

Authors and Affiliations

  1. Department of Psychology, University of Kentucky, Lexington, Ky., USA

    Anthony S. Rauhut, Nicole Neugebauer & Michael T. Bardo

  2. College of Pharmacy, University of Kentucky, Lexington, KY 40536, USA

    Linda P. Dwoskin

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  1. Anthony S. Rauhut
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  2. Nicole Neugebauer
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  3. Linda P. Dwoskin
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  4. Michael T. Bardo
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Correspondence to Linda P. Dwoskin.

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Rauhut, A.S., Neugebauer, N., Dwoskin, L.P. et al. Effect of bupropion on nicotine self-administration in rats. Psychopharmacology 169, 1–9 (2003). https://doi.org/10.1007/s00213-003-1450-x

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  • DOI: https://doi.org/10.1007/s00213-003-1450-x

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