Psychopharmacology

, Volume 169, Issue 1, pp 1–9 | Cite as

Effect of bupropion on nicotine self-administration in rats

  • Anthony S. Rauhut
  • Nicole Neugebauer
  • Linda P. Dwoskin
  • Michael T. Bardo
Original Investigation

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.

Keywords

Amphetamine Apomorphine Bupropion Methamphetamine Nicotine Self-administration 

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Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Anthony S. Rauhut
    • 1
    • 3
  • Nicole Neugebauer
    • 1
  • Linda P. Dwoskin
    • 2
  • Michael T. Bardo
    • 1
  1. 1.Department of PsychologyUniversity of KentuckyLexingtonUSA
  2. 2.College of PharmacyUniversity of KentuckyLexingtonUSA
  3. 3.Department of PsychologyDickinson CollegeCarlisleUSA

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