Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats

TY - JOUR

T1 - Chronic bupropion differentially alters the reinforcing, reward-enhancing and conditioned motivational properties of nicotine in rats

AU - Paterson, Neil E.

AU - Balfour, David J. K.

AU - Markou, Athina

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - SUSTAINED-RELEASE BUPROPION

KW - RANDOMIZED CONTROLLED-TRIAL

KW - BRAIN-STIMULATION REWARD

KW - RECEPTOR PARTIAL AGONIST

KW - SMOKING-CESSATION

KW - NUCLEUS-ACCUMBENS

KW - D-AMPHETAMINE

KW - EXTRACELLULAR DOPAMINE

KW - ABSTINENCE SYNDROME

KW - WITHDRAWAL

U2 - 10.1080/14622200802097571

DO - 10.1080/14622200802097571

M3 - Article

C2 - 18584463

SN - 1462-2203

VL - 10

SP - 995

EP - 1008

JO - Nicotine & Tobacco Research

JF - Nicotine & Tobacco Research

IS - 6

ER -