Tobacco smoking remains a leading cause of death and disability in the developed world. Many who wish to quit smoking are unable to do so. Although substantial advances have been made to identify neurobehavioral mechanisms underlying nicotine dependence, there is a great need to translate these findings into targeted, efficacious interventions, and to understand the mechanisms by which successful interventions exert their effects. Theoretical models and a growing empirical literature suggest that addictive disorders, including tobacco dependence, are characterized by mesolimbic hypersensitivity to smoking reward and related cues and hyposensitivity to nonsmoking rewards, particularly during the withdrawal that occurs during the early stages of a quit attempt. This dysregulated reward processing may represent a particular vulnerability for individuals with depressive symptoms that is likely to contribute to relapse and presents a promising target for intervention. The overarching goal of the research proposed in this application is to develop and evaluate a novel intervention that directly targets this reward processing imbalance by both a) decreasing smoking reinforcement through pretreatment with very low nicotine cigarettes (VLNC's) and b) increasing reinforcement from other non-drug rewards through behavioral activation (BA). The proposed research study has the following aims: 1) To examine the effects of BA + VLNC compared with VLNC only on mesolimbic reactivity and subjective sensitivity to smoking and monetary rewards among smokers with mild depressive symptoms; 2) To gather preliminary data on the effects of combined BA + VLNC on smoking cessation outcomes; and 3) To explore mediating and moderating effects of pre-and post-treatment brain function on smoking outcomes. The proposed research builds upon the Principle Investigator, Dr. Maggie Sweitzer's, previous experience and is closely aligned with her overarching career development goal of becoming an independent investigator with expertise in the development and evaluation of mechanistically-informed treatments for smoking cessation. Dr. Sweitzer is a clinical associate at Duke University Medical Center with expertise in behavioral pharmacology of smoking and functional neuroimaging. The primary training goals of this application are to gain skills in a) advanced neuroscience and neuroimaging methods; b) treatment development and evaluation; c) conducting clinical trials; and d) ethical and responsible conduct of research. The results of the proposed research and training plans will facilitate Dr. Sweitzer's development as an independent investigator and provide preliminary data for a future larger scale efficacy study.

Public Health Relevance

Cigarette smoking is a leading preventable cause of death and disability. Even when aided by standard smoking cessation treatments, the majority of quit attempts result in relapse. Cessation rates may be improved by developing rationally designed interventions that combine behavioral and pharmacological strategies to target mechanisms of dependence. The proposed research will lead to a better understanding of reward dysregulation as a mechanism underlying smoking behavior and may contribute to more efficacious smoking cessation treatments.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Risk, Prevention and Intervention for Addictions Study Section (RPIA)
Program Officer
Lao, Guifang
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Duke University
Schools of Medicine
United States
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Sweitzer, Maggie M; Kollins, Scott H; Kozink, Rachel V et al. (2018) ADHD, Smoking Withdrawal, and Inhibitory Control: Results of a Neuroimaging Study with Methylphenidate Challenge. Neuropsychopharmacology 43:851-858
Pacek, Lauren R; McClernon, F Joseph; Rass, Olga et al. (2018) Perceived risk of developing smoking-related disease among persons living with HIV. AIDS Care 30:1329-1334
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
Froeliger, Brett; McConnell, Patrick A; Bell, Spencer et al. (2017) Association Between Baseline Corticothalamic-Mediated Inhibitory Control and Smoking Relapse Vulnerability. JAMA Psychiatry 74:379-386
Stevenson, Jennifer G; Oliver, Jason A; Hallyburton, Matthew B et al. (2017) Smoking environment cues reduce ability to resist smoking as measured by a delay to smoking task. Addict Behav 67:49-52
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
Sweitzer, Maggie M; Geier, Charles F; Denlinger, Rachel et al. (2016) Blunted striatal response to monetary reward anticipation during smoking abstinence predicts lapse during a contingency-managed quit attempt. Psychopharmacology (Berl) 233:751-60
Sweitzer, Maggie M; Geier, Charles F; Addicott, Merideth A et al. (2016) Smoking Abstinence-Induced Changes in Resting State Functional Connectivity with Ventral Striatum Predict Lapse During a Quit Attempt. Neuropsychopharmacology 41:2521-9