The purpose of this study is to investigate the modulatory effects of acute and chronic nicotine exposure on reinforcement learning for monetary rewards. Nicotine, the primary addictive component in tobacco, is a weak reinforcer that does not induce robust euphoric effects like other drugs of abuse (e.g., cocaine, alcohol), yet produces a higher rate of dependence among tobacco users than among users of other addictive drugs. A potential explanation of this paradox is that nicotine amplifies the salience of other stimuli that have some incentive value and prolonged exposure could result in dysregulated reward processing. Reinforcement learning is the process of learning what actions to take to maximize reward, and may be the mechanism by which nicotine amplifies the incentive value of other stimuli. A key component of reinforcement learning is the prediction error, which is the difference between the actual and the expected reward outcome. Neuroimaging studies have shown that BOLD activation in the mesocorticolimbic pathway correlates with prediction errors during reinforcement learning paradigms. The overarching aim of this proposal is to use neuroeconomic models of reinforcement learning to study the acute and chronic effects of nicotine on motivational behavior and prediction error-related neural activation using a task with probabilistic outcomes and fMRI. Nonsmokers will be scanned following acute nicotine and placebo administration, and smokers will be scanned following normal smoking behavior and 24-hours of smoking abstinence. This proposal will bridge the gap in the literature between neuroeconomic and addiction research and these results will inform whether the initiation and maintenance of smoking behavior could be facilitated by the effects of nicotine on reinforcement learning. The Principal Investigator (PI) will be mentored and advised by a team of faculty with expertise in nicotine psychopharmacology, fMRI, and neuroeconomics. The institution provides exceptional facilities and departments dedicated to these three fields of research. In addition to learning how to design and conduct clinical nicotine research, this training plan with provide the PI with the opportunity to integrate several distinct, yet overlapping, fields of research in order to explore new approaches to understanding the etiology of nicotine addiction. This proposal builds upon the PI's previous pharmaco-MRI experience, and will allow her to develop new skills while contributing to research on the effects of nicotine on decision-making behavior in humans. The education, training, and research goals described in this proposal will provide the applicant with the research experience necessary to become a successful independent investigator.

Public Health Relevance

Cigarette smoking is a leading cause of death and disability in the United States, yet nicotine psychopharmacology does not entirely explain the addictiveness of tobacco. An important moderating factor may be the ability of nicotine to amplify the incentive value of other rewarding stimuli. This may play a critical role in the initiation, maintenance, and relapse of tobacco use. This study will lead to a better, more precise understanding of how nicotine shapes reward processing, which is believed to contribute to its abuse liability.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Scientist Development Award - Research & Training (K01)
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Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Bjork, James M
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Duke University
Schools of Medicine
United States
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Addicott, Merideth A; Daughters, Stacey B; Strauman, Timothy J et al. (2018) Distress tolerance to auditory feedback and functional connectivity with the auditory cortex. Psychiatry Res Neuroimaging 282:1-10
Addicott, Merideth A; Sweitzer, Maggie; McClernon, F Joseph (2018) The Effects of Nicotine and Tobacco use on Brain Reward Function: Interaction with Nicotine Dependence Severity. Nicotine Tob Res :
Addicott, M A; Pearson, J M; Sweitzer, M M et al. (2017) A Primer on Foraging and the Explore/Exploit Trade-Off for Psychiatry Research. Neuropsychopharmacology 42:1931-1939
Addicott, Merideth A; Oliver, Jason A; Joseph McClernon, F (2017) Nicotine increases anterior insula activation to expected and unexpected outcomes among nonsmokers. Psychopharmacology (Berl) 234:1145-1154
McClernon, F Joseph; Conklin, Cynthia A; Kozink, Rachel V et al. (2016) Hippocampal and Insular Response to Smoking-Related Environments: Neuroimaging Evidence for Drug-Context Effects in Nicotine Dependence. Neuropsychopharmacology 41:877-85
McClernon, Francis Joseph; Froeliger, Brett; Rose, Jed E et al. (2016) The effects of nicotine and non-nicotine smoking factors on working memory and associated brain function. Addict Biol 21:954-61
McClernon, F Joseph; Addicott, Merideth A; Sweitzer, Maggie M (2015) Smoking abstinence and neurocognition: implications for cessation and relapse. Curr Top Behav Neurosci 23:193-227
Addicott, Merideth A; Pearson, John M; Kaiser, Nicole et al. (2015) Suboptimal foraging behavior: a new perspective on gambling. Behav Neurosci 129:656-665
Addicott, Merideth A; Sweitzer, Maggie M; Froeliger, Brett et al. (2015) Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes. Neuropsychopharmacology 40:2648-56
Addicott, Merideth A; Pearson, John M; Froeliger, Brett et al. (2014) Smoking automaticity and tolerance moderate brain activation during explore-exploit behavior. Psychiatry Res 224:254-61

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