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)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-RXL-E (05))
Program Officer
Morgan, Glen D
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pennsylvania
Schools of Medicine
United States
Zip Code
Cole, Robert D; Poole, Rachel L; Guzman, Dawn M et al. (2015) Contributions of ?2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice. Psychopharmacology (Berl) 232:1207-17
Jain, Raka; Jhanjee, Sonali; Jain, Veena et al. (2014) A double-blind placebo-controlled randomized trial of varenicline for smokeless tobacco dependence in India. Nicotine Tob Res 16:50-7
Falcone, Mary; Wileyto, E Paul; Ruparel, Kosha et al. (2014) Age-related differences in working memory deficits during nicotine withdrawal. Addict Biol 19:907-17
Turner, J R; Ray, R; Lee, B et al. (2014) Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence. Mol Psychiatry 19:801-10
Ashare, Rebecca L; Falcone, Mary; Lerman, Caryn (2014) Cognitive function during nicotine withdrawal: Implications for nicotine dependence treatment. Neuropharmacology 76 Pt B:581-91
Hussmann, G Patrick; DeDominicis, Kristen E; Turner, Jill R et al. (2014) Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain. J Neurochem 129:721-31
Yohn, Nicole L; Turner, Jill R; Blendy, Julie A (2014) Activation of ?4?2*/?6?2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors. J Pharmacol Exp Ther 349:348-54
Ashare, Rebecca L; Schmidt, Heath D (2014) Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal. Expert Opin Drug Discov 9:579-94
Goelz, Patricia M; Audrain-McGovern, Janet E; Hitsman, Brian et al. (2014) The association between changes in alternative reinforcers and short-term smoking cessation. Drug Alcohol Depend 138:67-74
Poole, Rachel L; Connor, David A; Gould, Thomas J (2014) Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice. Behav Neurosci 128:588-93

Showing the most recent 10 out of 69 publications