Bupropion and Secondary Motivational Effects of Nicotine

Dickinson College, Carlisle PA

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Abstract

DESCRIPTION (provided by applicant): The primary (pharmacological) and secondary (conditioned) motivational (rewarding and aversive) properties of nicotine contribute to nicotine addiction. Human and rat studies have highlighted the importance of the primary and secondary rewarding properties of nicotine in the acquisition, maintenance, extinction, reinstatement and reacquisition of nicotine self-administration and the primary and secondary aversive properties of nicotine during periods of withdrawal - different stages of nicotine addiction. The efficacious antidepressant and smoking-cessation agent, bupropion, has been shown to increase nicotine self-administration in rats and smoking behavior in humans. Conversely, human smoking and rat intracranial self-stimulation studies have shown that bupropion attenuates the primary aversive properties associated with nicotine withdrawal and promotes smoking abstinence in humans. Studies also have shown that, following a period of nicotine withdrawal, bupropion attenuates the smoking-elicited "buzz" once smoking is reinitiated. Collectively, these human and rat studies suggest that bupropion enhances the primary rewarding properties of nicotine during periods of nicotine maintenance and ameliorates the primary aversive and rewarding properties of nicotine during periods of withdrawal and reinstatement, respectively. Little research, however, has determined the effect of bupropion on the secondary motivational properties of nicotine during different stages of nicotine addiction. Thus, the present proposal will determine the effect of bupropion on the secondary rewarding properties of nicotine during periods of acquisition and expression (Specific Aim 1), reinstatement and reacquisition (Specific Aim 2), and the secondary aversive properties of nicotine during periods of withdrawal (Specific Aim 3), using the conditioned place preference/aversion paradigm. Because the secondary motivational properties of nicotine are thought to contribute to the acquisition, maintenance, withdrawal, reinstatement, and reacquisition of smoking behavior in humans, the ability of bupropion to alter the secondary motivational properties of nicotine during different stages of nicotine addiction, may provide valuable clues as to its therapeutic mechanism of action and potentially contribute to the development of novel, more efficacious smoking-cessation agents; thus, helping to achieve the Healthy People 2010 objective of reducing adult and adolescent cigarette smoking in the U.S. population to 12% and 16%, accordingly.