Characterization of the effects of bupropion on the reinforcing properties of nicotine and food in rats.
Bupropion is an atypical antidepressant drug that is the only nonnicotine-based prescription medicine approved for smoking cessation by the Food and Drug Administration. The aim of the present experiments was to investigate the effects of bupropion (5-40 mg/kg) on the reinforcing properties of nicotine and food in rats. The effects of bupropion were studied under two schedules of reinforcement: a fixed ratio 5 time-out 20-sec (FR5 TO20 s) and a progressive ratio (PR). Rats were trained to respond for nicotine (0.01 or 0.03 mg/kg/infusion, free base) or food under the FR5 TO20 s schedule. Pretreatment with the highest dose of bupropion (40 mg/kg) resulted in a significant reduction (approximately 50%) of nicotine intake in rats self-administering 0.03 mg/kg/infusion of nicotine. The same dose of bupropion also decreased (approximately 40%) the self-administration of 0.01 mg/kg/infusion of nicotine, but this effect did not reach statistical significance. Pretreatment with bupropion slightly (approximately 15%) reduced responding for food under the FR5 TO20 s schedule. Finally, pretreatment with bupropion did not affect the self-administration of nicotine (0.03 mg/kg/infusion) under a PR schedule, but dose-dependently increased responding for food under the same PR schedule. These findings indicate that a high dose of bupropion decreases the reinforcing properties of nicotine as measured under an FR schedule, while having no apparent effects on breaking points for nicotine under a PR schedule that reflects both the reinforcing properties and the motivation to obtain nicotine.
Bruijnzeel
Adrie W
AW
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037, USA.
Markou
Athina
A
D000818:Animals; D016642:Bupropion / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects* / Q000502:physiology; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012201:Reward; D012646:Self Administration; D014029:Tobacco Use Disorder / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D018765:Dopamine Uptake Inhibitors; D016642:Bupropion; D009538:Nicotine