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. CENTER CHARACTERISTICS

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
1P50CA143187-01
Application #
7577025
Study Section
Special Emphasis Panel (ZDA1-RXL-E (05))
Program Officer
Morgan, Glen D
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
1
Fiscal Year
2009
Total Cost
$1,711,330
Indirect Cost
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Maurer, John J; Sandager-Nielsen, Karin; Schmidt, Heath D (2017) Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283. Psychopharmacology (Berl) 234:475-484
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
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
Ashare, Rebecca L; Lerman, Caryn; Cao, Wen et al. (2016) Nicotine withdrawal alters neural responses to psychosocial stress. Psychopharmacology (Berl) 233:2459-67
Falcone, Mary; Cao, Wen; Bernardo, Leah et al. (2016) Brain Responses to Smoking Cues Differ Based on Nicotine Metabolism Rate. Biol Psychiatry 80:190-7
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
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
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
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
Yildirim, Emre; Connor, David A; Gould, Thomas J (2015) ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice. Behav Pharmacol 26:241-8

Showing the most recent 10 out of 109 publications