title: Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats.
abstract: Bupropion is an effective anti-smoking agent in humans, but the behavioral mechanisms mediating this effect are unclear. The present studies assessed the effects of chronic bupropion on the reinforcing and reward-enhancing effects of self-administered nicotine, and on the motivational properties of a nicotine-associated conditioned reinforcer. The present studies also assessed the reward-enhancing effects of nicotine self-administration under different levels of access to nicotine, and the effects of enforced abstinence from self-administered nicotine on brain reward function and somatic signs. Rats were prepared with bipolar electrodes in the lateral hypothalamus and trained on a discrete trial intracranial self-stimulation (ICSS) task. After establishing stable ICSS thresholds, rats were prepared with intravenous catheters and allowed to self-administer nicotine at different levels of access. Self-administered nicotine lowered ICSS thresholds, thereby providing a measure of the reward-enhancing effects of nicotine. Abstinence from 6h/d 7d/wk nicotine self-administration was associated with increased somatic signs of nicotine withdrawal and unchanged brain reward thresholds. Chronic bupropion administration via subcutaneous osmotic minipump had no effect on nicotine self-administration, but attenuated nicotine-induced enhancement of brain reward function and enhanced the motivational properties of a previously nicotine-associated conditioned stimulus. Thus, it is unlikely that chronic bupropion exerts anti-smoking effects by attenuating the primary or conditioned reinforcing effects of nicotine. Rather, preclinical investigations suggest that bupropion attenuates nicotine-induced enhancement of brain reward function and reverses the anhedonic, somatic, and neurochemical correlates of nicotine withdrawal.
authors.affiliation: Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA 92093-0603, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Paterson
authors.forename: David J K
authors.initials: DJ
authors.lastname: Balfour
authors.forename: Athina
authors.initials: A
authors.lastname: Markou
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D001921:Brain / Q000187:drug effects*; D016642:Bupropion / Q000008:administration & dosage*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004334:Drug Administration Schedule; D004558:Electric Stimulation; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology; D012201:Reward; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology
chemical_list: D018687:Antidepressive Agents, Second-Generation; D011978:Receptors, Nicotinic; D016642:Bupropion; D009538:Nicotine