Bupropion and nicotine enhance responding for nondrug reinforcers via dissociable pharmacological mechanisms in rats
- 168 Downloads
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.
KeywordsNicotine 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.
- Borges V, Yang E, Dunn J, Henion J (2004) High-throughput liquid chromatography-tandem mass spectrometry determination of bupropion and its metabolites in human, mouse and rat plasma using a monolithic column. J Chromatogr, B, Analytical Technologies in the Biomedical and Life Sciences 804:277–287CrossRefGoogle Scholar
- Chaudhri N, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, Palmatier MI, Liu X, Sved AF (2006a) Operant responding for conditioned and unconditioned reinforcers in rats is differentially enhanced by the primary reinforcing and reinforcement-enhancing effects of nicotine. Psychopharmacology 189:27–36CrossRefPubMedGoogle Scholar
- Chu B, Kelley AE (1992) Potentiation of reward-related responding by psychostimulant infusion into nucleus accumbens: role of dopamine receptor subtypes. Psychobiology 20:153–162Google Scholar
- Donny EC, Chaudhri N, Caggiula AR, Evans-Martin FF, Booth S, Gharib MA, Clements LA, Sved AF (2003) Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement. Psychopharmacology 169:68–76CrossRefPubMedGoogle Scholar
- Liu X, Caggiula AR, Palmatier MI, Booth S, Gharib M, Craven L, Donny EC, Sved AF (2006) Reinforcement enhancing effect of nicotine and its attenuation by nicotinic and dopaminergic antagonists. Proceedings of the Society for Research on Nicotine and TobaccoGoogle Scholar
- Liu X, Palmatier MI, Caggiula AR, Donny EC, Booth S, Gharib M, Craven L, Sved AF (2007) Cholinergic substrates of the reinforcement enhancing effects of nicotine. Psychopharmacology SubmittedGoogle Scholar
- McGehee DS (2007) Nicotine and synaptic plasticity in prefrontal cortex. Sci STKE 2007: pe44Google Scholar
- Palmatier MI, Evans-Martin FF, Hoffman A, Caggiula AR, Chaudhri N, Donny EC, Liu X, Booth S, Gharib M, Craven L, Sved AF (2006) Dissociating the primary reinforcing and reinforcement-enhancing effects of nicotine using a rat self-administration paradigm with concurrently available drug and environmental reinforcers. Psychopharmacology 184:391–400CrossRefPubMedGoogle Scholar
- Palmatier MI, Matteson GL, Black JJ, Liu X, Caggiula AR, Craven L, Donny EC, Sved AF (2007c) The reinforcement enhancing effects of nicotine depend on the incentive value of non-drug reinforcers and increase with repeated drug injections. Drug Alcohol DependGoogle Scholar
- Schuster CR, Lucchesi BR, Emley GS (1979) The effects of d-amphetamine, meprobamate, and lobeline on the cigarette smoking behavior of normal human subjects. NIDA Res Monogr: 91–99Google Scholar
- Stairs DJ, Dworkin SI (2008) Rate-dependent effects of bupropion on nicotine self-administration and food-maintained responding in rats. Pharmacol Biochem BehavGoogle Scholar
- Thanos PK, Michaelides M, Ho CW, Wang GJ, Newman AH, Heidbreder CA, Ashby CR Jr, Gardner EL, Volkow ND (2008) The effects of two highly selective dopamine D3 receptor antagonists (SB-277011A and NGB-2904) on food self-administration in a rodent model of obesity. Pharmacol Biochem Behav 89:499–507CrossRefPubMedGoogle Scholar