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Grant Details

Grant Number: 5P50AA015632-10 Interpret this number
Primary Investigator: O'Malley, Stephanie
Organization: Yale University
Project Title: Tobacco Dependence & Risk Factors for Treatment Failure
Fiscal Year: 2008
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Abstract

DESCRIPTION (provided by applicant): Many current smokers show several risk factors that make smoking cessation more difficult. We propose to study the biological basis underlying how risk factors might lead to relapse to smoking. Some predictors of treatment failure for smoking cessation include weight concerns, heavy alcohol use, and female gender. This proposal will use animal models to determine how nicotine affects biological processes related to these risk factors, and will focus on how neuronal nicotinic acetylcholine receptors (nAChRs) can affect behavioral and biochemical responses related to these risk factors. These experiments will make use of pharmacological studies in normal rodents as well as experiments with mice lacking the beta2 subunit of the nAChR, transgenic lines with selective expression of these nAChRs in particular brain regions and knockout mice lacking the neuropeptides CART, galanin and NPY which have previously been generated. The aims of this project are: 1) to follow up on previous studies identifying second messenger pathways affected by nicotine treatment by using viral vector and local infusion strategies, identifying functional effects of these molecular changes on behaviors related to nicotine addiction; 2) to determine the relationship between nicotine, food intake, expression of hypothalamic peptides and appetitive behaviors in normal mice and rats undergoing behavioral paradigms following nicotine treatment, and in knockout mice lacking hypothalamic peptides related to feeding (the effect of naltrexone on these parameters will also be investigated); 3) to identify sex differences in these behavioral and neurochemical effects; 4) and to determine the concurrent and independent effects of chronic ethanol and nicotine treatment on biochemical and behavioral responses in appetitive behaviors. These experiments will contribute to the scientific background necessary for designing new strategies for treatment of smokers resistant to current cessation methods.

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Publications

Repeated nicotine exposure during adolescence alters reward-related learning in male and female rats.
Authors: Quick SL, Olausson P, Addy NA, Taylor JR
Source: Behav Brain Res, 2014 Mar 15;261, p. 171-6.
EPub date: 2013 Dec 12.
PMID: 24333376
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Menthol cigarette use predicts treatment outcomes of weight-concerned smokers.
Authors: Rojewski AM, Toll BA, O'Malley SS
Source: Nicotine Tob Res, 2014 Jan;16(1), p. 115-9.
EPub date: 2013 Oct 10.
PMID: 24113927
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Mediating role of stress reactivity in the effects of prenatal tobacco exposure on childhood mental health outcomes.
Authors: Park A, O'Malley SS, King SL, Picciotto MR
Source: Nicotine Tob Res, 2014 Feb;16(2), p. 174-85.
EPub date: 2013 Aug 29.
PMID: 23990474
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An exploratory pilot study of the relationship between neural correlates of cognitive control and reduction in cigarette use among treatment-seeking adolescent smokers.
Authors: Krishnan-Sarin S, Balodis IM, Kober H, Worhunsky PD, Liss T, Xu J, Potenza MN
Source: Psychol Addict Behav, 2013 Jun;27(2), p. 526-32.
EPub date: 2013 Apr 15.
PMID: 23586458
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Pubertal status, sensation-seeking, impulsivity, and substance use in high school-aged boys and girls.
Authors: Kong G, Smith AE, McMahon TJ, Cavallo DA, Schepis TS, Desai RA, Potenza MN, Krishnan-Sarin S
Source: J Addict Med, 2013 Mar-Apr;7(2), p. 116-21.
PMID: 23370933
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Sex differences in availability of ?2*-nicotinic acetylcholine receptors in recently abstinent tobacco smokers.
Authors: Cosgrove KP, Esterlis I, McKee SA, Bois F, Seibyl JP, Mazure CM, Krishnan-Sarin S, Staley JK, Picciotto MR, O'Malley SS
Source: Arch Gen Psychiatry, 2012 Apr;69(4), p. 418-27.
PMID: 22474108
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The relationship between age of gambling onset and adolescent problematic gambling severity.
Authors: Rahman AS, Pilver CE, Desai RA, Steinberg MA, Rugle L, Krishnan-Sarin S, Potenza MN
Source: J Psychiatr Res, 2012 May;46(5), p. 675-83.
EPub date: 2012 Mar 10.
PMID: 22410208
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Gender differences in adolescent marijuana use and associated psychosocial characteristics.
Authors: Schepis TS, Desai RA, Cavallo DA, Smith AE, McFetridge A, Liss TB, Potenza MN, Krishnan-Sarin S
Source: J Addict Med, 2011 Mar;5(1), p. 65-73.
PMID: 21769049
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Reduced locomotor responses to cocaine in ghrelin-deficient mice.
Authors: Abizaid A, Mineur YS, Roth RH, Elsworth JD, Sleeman MW, Picciotto MR, Horvath TL
Source: Neuroscience, 2011 Sep 29;192, p. 500-6.
EPub date: 2011 Jun 12.
PMID: 21699961
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Nicotine decreases food intake through activation of POMC neurons.
Authors: Mineur YS, Abizaid A, Rao Y, Salas R, DiLeone RJ, Gündisch D, Diano S, De Biasi M, Horvath TL, Gao XB, Picciotto MR
Source: Science, 2011 Jun 10;332(6035), p. 1330-2.
PMID: 21659607
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Shopping problems among high school students.
Authors: Grant JE, Potenza MN, Krishnan-Sarin S, Cavallo DA, Desai RA
Source: Compr Psychiatry, 2011 May-Jun;52(3), p. 247-52.
PMID: 21497217
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Effect of night smoking, sleep disturbance, and their co-occurrence on smoking outcomes.
Authors: Peters EN, Fucito LM, Novosad C, Toll BA, O'Malley SS
Source: Psychol Addict Behav, 2011 Jun;25(2), p. 312-9.
PMID: 21443301
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Stealing among high school students: prevalence and clinical correlates.
Authors: Grant JE, Potenza MN, Krishnan-Sarin S, Cavallo DA, Desai RA
Source: J Am Acad Psychiatry Law, 2011;39(1), p. 44-52.
PMID: 21389165
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A preliminary investigation of varenicline for heavy drinking smokers.
Authors: Fucito LM, Toll BA, Wu R, Romano DM, Tek E, O'Malley SS
Source: Psychopharmacology (Berl), 2011 Jun;215(4), p. 655-63.
EPub date: 2011 Jan 11.
PMID: 21221531
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Imaging receptor changes in human drug abusers.
Authors: Cosgrove KP
Source: Curr Top Behav Neurosci, 2010;3, p. 199-217.
PMID: 21161754
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The nicotinic acetylcholine receptor partial agonist varenicline increases the ataxic and sedative-hypnotic effects of acute ethanol administration in C57BL/6J mice.
Authors: Kamens HM, Andersen J, Picciotto MR
Source: Alcohol Clin Exp Res, 2010 Dec;34(12), p. 2053-60.
EPub date: 2010 Oct 14.
PMID: 20946306
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Effect of binge eating on treatment outcomes for smoking cessation.
Authors: White MA, Peters EN, Toll BA
Source: Nicotine Tob Res, 2010 Nov;12(11), p. 1172-5.
EPub date: 2010 Oct 1.
PMID: 20889472
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Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues.
Authors: Löf E, Olausson P, Stomberg R, Taylor JR, Söderpalm B
Source: Psychopharmacology (Berl), 2010 Oct;212(3), p. 321-8.
EPub date: 2010 Jul 31.
PMID: 20676610
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Quantification of smoking-induced occupancy of beta2-nicotinic acetylcholine receptors: estimation of nondisplaceable binding.
Authors: Esterlis I, Cosgrove KP, Batis JC, Bois F, Stiklus SM, Perkins E, Seibyl JP, Carson RE, Staley JK
Source: J Nucl Med, 2010 Aug;51(8), p. 1226-33.
EPub date: 2010 Jul 21.
PMID: 20660383
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Smoking expectancies, weight concerns, and dietary behaviors in adolescence.
Authors: Cavallo DA, Smith AE, Schepis TS, Desai R, Potenza MN, Krishnan-Sarin S
Source: Pediatrics, 2010 Jul;126(1), p. e66-72.
EPub date: 2010 Jun 14.
PMID: 20547649
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Low-dose naltrexone augmentation of nicotine replacement for smoking cessation with reduced weight gain: a randomized trial.
Authors: Toll BA, White M, Wu R, Meandzija B, Jatlow P, Makuch R, O'Malley SS
Source: Drug Alcohol Depend, 2010 Oct 1;111(3), p. 200-6.
EPub date: 2010 Jun 12.
PMID: 20542391
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Nicotine dependence as a moderator of message framing effects on smoking cessation outcomes.
Authors: Fucito LM, Latimer AE, Salovey P, Toll BA
Source: Ann Behav Med, 2010 Jun;39(3), p. 311-7.
PMID: 20502997
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Decreased Beta(2)*-nicotinic acetylcholine receptor availability after chronic ethanol exposure in nonhuman primates.
Authors: Cosgrove KP, Kloczynski T, Bois F, Pittman B, Tamagnan G, Seibyl JP, Krystal JH, Staley JK
Source: Synapse, 2010 Sep;64(9), p. 729-32.
PMID: 20340174
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Quitting smoking and change in alcohol consumption in the International Tobacco Control (ITC) Four Country Survey.
Authors: Kahler CW, Borland R, Hyland A, McKee SA, O'Connor RJ, Fong GT, Cummings KM
Source: Drug Alcohol Depend, 2010 Jul 1;110(1-2), p. 101-7.
EPub date: 2010 Mar 15.
PMID: 20227840
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