Abstinence from smoking produces aversive symptoms that prompt relapse, often within the first week following a quit attempt. Clarifying the neurobiological and behavioral underpinnings of these early abstinence symptoms is, therefore, critical to develop more efficacious treatments. The proposed Center for Interdisciplinary Research on Nicotine Addiction (CIRNA) extends nine years of research conducted in the Transdisciplinary Tobacco Use Research Center (TTURC) at UPENN. Spanning from preclinical to clinical studies, CIRNA includes a highly interactive set of projects and cores that seek to: (1) discover the cellular, molecular, neural, and behavioral basis of early nicotine abstinence effects that contribute to relapse;(2) identify brain and behavioral mechanisms through which efficacious therapies modulate these processes;and (3) validate novel medication screening approaches. Project 1 uses neurobiology and pharmacology to elucidate the molecular and behavioral basis of emotional and cognitive symptoms of nicotine abstinence and re-exposure in a mouse model. Project 2 uses electrophysiology and pharmacology to explore the effects of nicotine abstinence and re-exposure on sensory processing in key brain regions in mice. Project 3 uses human neuroimaging to examine the neural substrates of early abstinence symptoms and medication response. Project 4 extends this work by validating novel approaches to improve the sensitivity of early human medication screening paradigms for nicotine dependence. Shared resources, including an Administrative Core, a Data Management and Biostatistics Core, and a Biospecimen Core provide value-added, as well as support for a comprehensive data sharing plan. A Career Development Core promotes involvement of post-doctoral fellows and junior investigators in these projects, and supports pilot projects to facilitate career development. Thus, the CIRNA addresses the clinically important problem of nicotine dependence using innovative multidisciplinary approaches, with the ultimate goal of developing more efficacious medications for tobacco dependence and prevention of tobacco-related disease. The CIRNA is proposed to replace the TTURC, since this NIH initiative is ending.

Public Health Relevance

The proposed Center will generate new knowledge of the biological and behavioral bases of early nicotine abstinence symptoms that contribute to smoking relapse, and will study how efficacious medications reverse these processes. This information will be valuable to develop more effective medications to treat nicotine dependence.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center (P50)
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Special Emphasis Panel (ZDA1-RXL-E (05))
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Morgan, Glen D
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University of Pennsylvania
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Ashare, Rebecca L; Lerman, Caryn; Cao, Wen et al. (2016) Nicotine withdrawal alters neural responses to psychosocial stress. Psychopharmacology (Berl) 233:2459-67
Forcelli, Patrick A; Turner, Jill R; Lee, Bridgin G et al. (2016) Anxiolytic- and antidepressant-like effects of the methadone metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP). Neuropharmacology 101:46-56
Schnoll, Robert A; Hitsman, Brian; Blazekovic, Sonja et al. (2016) Longitudinal changes in smoking abstinence symptoms and alternative reinforcers predict long-term smoking cessation outcomes. Drug Alcohol Depend 165:245-52
Strasser, Andrew A; Souprountchouk, Valentina; Kaufmann, Amanda et al. (2016) Nicotine Replacement, Topography, and Smoking Phenotypes of E-cigarettes. Tob Regul Sci 2:352-362
Perkins, Kenneth A; Karelitz, Joshua L; Michael, Valerie C et al. (2016) Initial Evaluation of Fenofibrate for Efficacy in Aiding Smoking Abstinence. Nicotine Tob Res 18:74-8
Ashare, R L; Kimmey, B A; Rupprecht, L E et al. (2016) Repeated administration of an acetylcholinesterase inhibitor attenuates nicotine taking in rats and smoking behavior in human smokers. Transl Psychiatry 6:e713
Lee, Bridgin G; Anastasia, Agustin; Hempstead, Barbara L et al. (2015) Effects of the BDNF Val66Met Polymorphism on Anxiety-Like Behavior Following Nicotine Withdrawal in Mice. Nicotine Tob Res 17:1428-35
Falcone, M; Bansal-Travers, M; Sanborn, P M et al. (2015) Awareness of FDA-mandated cigarette packaging changes among smokers of 'light' cigarettes. Health Educ Res 30:81-6
Jhanjee, Sonali; Jain, Raka; Jain, Veena et al. (2015) Evaluating the Effects of Varenicline on Craving, Withdrawal, and Affect in a Randomized, Double-Blind, Placebo-Controlled Clinical Trial of Varenicline for Smokeless Tobacco Dependence in India. J Psychoactive Drugs 47:325-30
Jain, Raka; Jhanjee, Sonali; Jain, Veena et al. (2015) Biochemical Validation of Self-Reported Smokeless Tobacco Abstinence among Smokeless Tobacco Users: Results from a Clinical Trial of Varenicline in India. J Psychoactive Drugs 47:331-5

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