, Volume 207, Issue 3, pp 381–390 | Cite as

Bupropion and nicotine enhance responding for nondrug reinforcers via dissociable pharmacological mechanisms in rats

  • Matthew I. Palmatier
  • Melissa E. Levin
  • Kara L. Mays
  • Eric C. Donny
  • Anthony R. Caggiula
  • Alan F. Sved
Original Investigation



Nicotine serves as a primary reinforcer but also potently enhances responding for nonnicotine stimuli with reinforcing properties. One of the most successful pharmacotherapies for smoking cessation, bupropion, also increases responding for nondrug reinforcers such as food and brain stimulation rewards.


The present studies investigated whether treatment with bupropion and nicotine had similar effects on responding for a reinforcing visual stimulus (VS). They also investigated whether the effects of bupropion and nicotine depended on common pharmacological substrates.


Nicotine (0.4 mg/kg base) enhanced responding for the VS, and this enhancing effect increased across testing sessions, replicating our previous findings. Bupropion (3, 10, and 30 mg/kg salt) dose-dependently increased responding for the VS. Treatment with 10 and 30 mg/kg bupropion resulted in a profile similar to nicotine; operant responding increased over repeated drug treatments. The reinforcement enhancing effect of nicotine, but not bupropion, was blocked by pretreatment with the nicotinic acetylcholine receptor antagonist mecamylamine. In contrast, the reinforcement enhancing effect of bupropion, but not nicotine, was blocked by pretreatment with the alpha noradrenergic antagonist prazosin.


The reinforcement enhancing effects of nicotine and bupropion increased over time and repeated treatments suggesting a shared mechanism of action. However, the reinforcement enhancing effects of nicotine are mediated by nicotinic acetylcholine receptors, whereas the reinforcement enhancing effects of bupropion were mediated by alpha noradrenergic receptors.


Nicotine Bupropion Operant conditioning Self-administration Dopamine Acetylcholine Norepinephrine 



All experiments followed the “Principles of laboratory animal care” (NIH #85-23, revised 1985) and were approved by the University of Pittsburgh Institutional Animal Care and Use Committee (Assurance # A3187-01). This research was supported by NIH grants, DA-24801, DA-10464, and DA-19278.


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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Matthew I. Palmatier
    • 1
  • Melissa E. Levin
    • 2
  • Kara L. Mays
    • 3
  • Eric C. Donny
    • 2
  • Anthony R. Caggiula
    • 2
  • Alan F. Sved
    • 3
  1. 1.Department of PsychologyKansas State UniversityManhattanUSA
  2. 2.Department of PsychologyUniversity of PittsburghPittsburghUSA
  3. 3.Department of NeuroscienceUniversity of PittsburghPittsburghUSA

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