Effect of bupropion on nicotine self-administration in rats.
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.
Rauhut
Anthony S
AS
Department of Psychology, University of Kentucky, Lexington, Ky. 40536, USA.
Neugebauer
Nicole
N
Dwoskin
Linda P
LP
Bardo
Michael T
MT
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000008:administration & dosage / Q000494:pharmacology; D016642:Bupropion / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
D000928:Antidepressive Agents; D000697:Central Nervous System Stimulants; D018491:Dopamine Agonists; D011978:Receptors, Nicotinic; D016642:Bupropion; D008694:Methamphetamine; D013395:Sucrose; D009538:Nicotine; D001058:Apomorphine