Effect of bupropion on nicotine self-administration in rats

• Published in: Psychopharmacologia 2003-08, Vol.169 (1), p.1-9
• Main Authors: RAUHUT, Anthony S, NEUGEBAUER, Nicole, DWOSKIN, Linda P, BARDO, Michael T
• Format: Article
• Language: English
• Subjects: Animals; Antidepressive Agents - pharmacology; Apomorphine - administration & dosage; Apomorphine - pharmacology; Biological and medical sciences; Bupropion - pharmacology; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Dopamine Agonists - pharmacology; Dose-Response Relationship, Drug; Male; Medical sciences; Methamphetamine - administration & dosage; Methamphetamine - pharmacology; Neuropharmacology; Nicotine - administration & dosage; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Nicotinic - drug effects; Self Administration; Sucrose - administration & dosage; Tobacco, tobacco smoking; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-003-1450-x

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. 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. 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. 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.