|Grant Number:||5P50CA143187-04 Interpret this number|
|Primary Investigator:||Lerman, Caryn|
|Organization:||University Of Pennsylvania|
|Project Title:||Center for Interdisciplinary Research on Nicotine Addiction (CIRNA)|
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.
Contributions of ?2 subunit-containing nAChRs to chronic nicotine-induced alterations in cognitive flexibility in mice.
Authors: Cole RD, Poole RL, Guzman DM, Gould TJ, Parikh V
Source: Psychopharmacology (Berl), 2014 Oct 4;null, p. null.
EPub date: 2014 Oct 4.
Administration of the nicotinic acetylcholine receptor agonists ABT-089 and ABT-107 attenuates the reinstatement of nicotine-seeking behavior in rats.
Authors: Lee AM, Arreola AC, Kimmey BA, Schmidt HD
Source: Behav Brain Res, 2014 Nov 1;274, p. 168-75.
EPub date: 2014 Aug 14.
Donepezil reverses nicotine withdrawal-induced deficits in contextual fear conditioning in C57BL/6J mice.
Authors: Poole RL, Connor DA, Gould TJ
Source: Behav Neurosci, 2014 Oct;128(5), p. 588-93.
EPub date: 2014 Jun 9.
Optimizing treatments for nicotine dependence by increasing cognitive performance during withdrawal.
Authors: Ashare RL, Schmidt HD
Source: Expert Opin Drug Discov, 2014 Jun;9(6), p. 579-94.
EPub date: 2014 Apr 7.
Activation of ?4?2*/?6?2* nicotinic receptors alleviates anxiety during nicotine withdrawal without upregulating nicotinic receptors.
Authors: Yohn NL, Turner JR, Blendy JA
Source: J Pharmacol Exp Ther, 2014 May;349(2), p. 348-54.
EPub date: 2014 Mar 13.
Large-scale brain network coupling predicts acute nicotine abstinence effects on craving and cognitive function.
Authors: Lerman C, Gu H, Loughead J, Ruparel K, Yang Y, Stein EA
Source: JAMA Psychiatry, 2014 May;71(5), p. 523-30.
The association between changes in alternative reinforcers and short-term smoking cessation.
Authors: Goelz PM, Audrain-McGovern JE, Hitsman B, Leone FT, Veluz-Wilkins A, Jepson C, Wileyto EP, D'Avanzo PA, Rivera JG, Schnoll RA
Source: Drug Alcohol Depend, 2014 May 1;138, p. 67-74.
EPub date: 2014 Feb 15.
Dissociation of tolerance and nicotine withdrawal-associated deficits in contextual fear.
Authors: Gould TJ, Wilkinson DS, Yildirim E, Blendy JA, Adoff MD
Source: Brain Res, 2014 Apr 22;1559, p. 1-10.
EPub date: 2014 Mar 2.
Chronic sazetidine-A maintains anxiolytic effects and slower weight gain following chronic nicotine without maintaining increased density of nicotinic receptors in rodent brain.
Authors: Hussmann GP, DeDominicis KE, Turner JR, Yasuda RP, Klehm J, Forcelli PA, Xiao Y, Richardson JR, Sahibzada N, Wolfe BB, Lindstrom J, Blendy JA, Kellar KJ
Source: J Neurochem, 2014 May;129(4), p. 721-31.
EPub date: 2014 Feb 7.
An efficient early phase 2 procedure to screen medications for efficacy in smoking cessation.
Authors: Perkins KA, Lerman C
Source: Psychopharmacology (Berl), 2014 Jan;231(1), p. 1-11.
EPub date: 2013 Dec 3.
Evidence from mouse and man for a role of neuregulin 3 in nicotine dependence.
Authors: Turner JR, Ray R, Lee B, Everett L, Xiang J, Jepson C, Kaestner KH, Lerman C, Blendy JA
Source: Mol Psychiatry, 2014 Jul;19(7), p. 801-10.
EPub date: 2013 Sep 3.
Individual differences in positivity offset and negativity bias: Gender-specific associations with two serotonin receptor genes.
Authors: Ashare RL, Norris CJ, Wileyto EP, Cacioppo JT, Strasser AA
Source: Pers Individ Dif, 2013 Sep 1;55(5), p. 469-473.
Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning.
Authors: Gould TJ, Leach PT
Source: Neurobiol Learn Mem, 2014 Jan;107, p. 108-32.
EPub date: 2013 Aug 22.
A double-blind placebo-controlled randomized trial of varenicline for smokeless tobacco dependence in India.
Authors: Jain R, Jhanjee S, Jain V, Gupta T, Mittal S, Goelz P, Wileyto EP, Schnoll RA
Source: Nicotine Tob Res, 2014 Jan;16(1), p. 50-7.
EPub date: 2013 Aug 14.
Neuroimaging in psychiatric pharmacogenetics research: the promise and pitfalls.
Authors: Falcone M, Smith RM, Chenoweth MJ, Bhattacharjee AK, Kelsoe JR, Tyndale RF, Lerman C, Pharmacogenomics Research Network Central Nervous System Working Group
Source: Neuropsychopharmacology, 2013 Nov;38(12), p. 2327-37.
EPub date: 2013 Jun 24.
Sensitivity and specificity of a procedure for early human screening of novel smoking cessation medications.
Authors: Perkins KA, Lerman C, Karelitz JL, Jao NC, Chengappa KN, Sparks GM
Source: Addiction, 2013 Nov;108(11), p. 1962-8.
EPub date: 2013 Jul 12.
Effects of bupropion on cognitive performance during initial tobacco abstinence.
Authors: Perkins KA, Karelitz JL, Jao NC, Gur RC, Lerman C
Source: Drug Alcohol Depend, 2013 Nov 1;133(1), p. 283-6.
EPub date: 2013 May 31.
Extrasynaptic targeting of NMDA receptors following D1 dopamine receptor activation and cocaine self-administration.
Authors: Ortinski PI, Turner JR, Pierce RC
Source: J Neurosci, 2013 May 29;33(22), p. 9451-61.