Title

Effect of Bupropion on Nicotine Self-Administration in Rats

Authors

Anthony S. Rauhut, Dickinson College
Nicole Neugebauer
Linda P. Dwoskin
Michael T. Bardo

Document Type

Article

Publication Date

8-2003

Department

Psychology

Language

English

Publication Title

Psychopharmacology

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.

Comments

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Recommended Citation

Rauhut, Anthony S., Nicole Neugebauer, Linda P. Dwoskin, and Michael T. Bardo. "Effect of Bupropion on Nicotine Self-Administration in Rats." Psychopharmacology 169, no. 1 (2003): 1-9.