Grant Number:	5P01CA075581-03 Interpret this number
Primary Investigator:	Pomerleau, Ovide
Organization:	University Of Michigan At Ann Arbor
Project Title:	Neuroscience of Nicotine Dependence and Cofactors
Fiscal Year:	1999

The goal of this Program Project application is to further the understanding of the human neurobiology of nicotine by examining brain mechanisms and behaviors that define nicotine dependence. it consists of 4 closely coordinated research projects adopting 3 approaches to further these aims: Imaging--to specify nicotine's locus of action in the normal human brain using PET; Psychopharmacology--to examine how cognitive deficits associated with psychiatric cofactors can reinforce (and overdetermine) smoking; and Behavioral genetics -- to increase knowledge about the heritability of nicotine's reinforcing effects via behavioral genetics research on individual differences in nicotine sensitivity and metabolism. Research Projects will test these hypotheses: Project 1: Acute nicotine doses will cause reliable regional changes in cerebral bloodflow and metabolism; Project 2: Where nicotine withdrawal effects overlap with ADHD symptomatology, affected individuals will experience severe and persistent nicotine abstinence symptomatology, which will be reduced by methylphenidate administration; neither diagnostic nor medication status will affect nicotine sensitivity; Project 3: Genetic influences on nicotine use can be partitioned into influences associated with cofactors (depression, childhood conduct disorder, ADHD) and influences associated with nicotine sensitivity; Project 4: Individual differences in nicotine disposition and kinetics are heritable; metabolic differences can be differentiated from environmental factors associated with smoking. Support will be provided by 3 Cores: The Administrative Core will facilitate communication, integration, and shared mission as well as ensure quality control; oversight will be provided by an External Advisory Board, which will meet annually to review progress and policy, and an Internal Advisory board, which will meet quarterly to advise on progress and use of resources. The Assessment Services Core will provide standardized assessment of nicotine dependence and cofactors across projects. The Assay Services Core will conduct nicotine/cotinine and other assays needed by the Research Projects. Health Significance: Cigarette smoking is associated with over 400,000 premature deaths per year in the U.S. Over the past decade, there has been substantial progress in defining mechanisms for nicotine reinforcement at the molecular and animal level; understanding aat the human level, however, has lagged behind. The long-term objective is to help redress this deficiency. A larger implication is that the widespread use of nicotine and its potent pharmacology make it an excellent model of drug abuse in general.




Validity of recall of tobacco use in two prospective cohorts.
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EPub date: 2010-10-01 00:00:00.0.
PMID: 20720099
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Test-retest reliability of web-based retrospective self-report of tobacco exposure and risk.
Authors: Brigham J. , Lessov-Schlaggar C.N. , Javitz H.S. , Krasnow R.E. , McElroy M. , Swan G.E. .
Source: Journal Of Medical Internet Research, 2009-08-11 00:00:00.0; 11(3), p. e35.
EPub date: 2009-08-11 00:00:00.0.
PMID: 19674962
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Association of tobacco dependence and quit attempt duration with Rasch-modeled withdrawal sensitivity using retrospective measures.
Authors: Javitz H.S. , Brigham J. , Lessov-Schlaggar C.N. , Krasnow R.E. , Swan G.E. .
Source: Addiction (abingdon, England), 2009 Jun; 104(6), p. 1027-35.
PMID: 19392910
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Reliability of adult retrospective recall of lifetime tobacco use.
Authors: Brigham J. , Lessov-Schlaggar C.N. , Javitz H.S. , McElroy M. , Krasnow R. , Swan G.E. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2008 Feb; 10(2), p. 287-99.
PMID: 18236293
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Exploring the inter-relationship of smoking age-at-onset, cigarette consumption and smoking persistence: genes or environment?
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Cohort trends in prevalence and spousal concordance for smoking.
Authors: Kuo P.H. , Wood P. , Morley K.I. , Madden P. , Martin N.G. , Heath A.C. .
Source: Drug And Alcohol Dependence, 2007-05-11 00:00:00.0; 88(2-3), p. 122-9.
EPub date: 2007-05-11 00:00:00.0.
PMID: 17055671
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Genome-wide scan for blood pressure in Australian and Dutch subjects suggests linkage at 5P, 14Q, and 17P.
Authors: Hottenga J.J. , Whitfield J.B. , Posthuma D. , Willemsen G. , de Geus E.J. , Martin N.G. , Boomsma D.I. .
Source: Hypertension, 2007 Apr; 49(4), p. 832-8.
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A possible smoking susceptibility locus on chromosome 11p12: evidence from sex-limitation linkage analyses in a sample of Australian twin families.
Authors: Morley K.I. , Medland S.E. , Ferreira M.A. , Lynskey M.T. , Montgomery G.W. , Heath A.C. , Madden P.A. , Martin N.G. .
Source: Behavior Genetics, 2006 Jan; 36(1), p. 87-99.
PMID: 16365831
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Validity of retrospective assessments of nicotine dependence: a preliminary report.
Authors: Hudmon K.S. , Pomerleau C.S. , Brigham J. , Javitz H. , Swan G.E. .
Source: Addictive Behaviors, 2005 Mar; 30(3), p. 613-7.
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The epidemiology and genetics of smoking initiation and persistence: crosscultural comparisons of twin study results.
Authors: Madden P.A. , Pedersen N.L. , Kaprio J. , Koskenvuo M.J. , Martin N.G. .
Source: Twin Research : The Official Journal Of The International Society For Twin Studies, 2004 Feb; 7(1), p. 82-97.
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A multidimensional model for characterizing tobacco dependence.
Authors: Hudmon K.S. , Marks J.L. , Pomerleau C.S. , Bolt D.M. , Brigham J. , Swan G.E. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2003 Oct; 5(5), p. 655-64.
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Development and validation of a self-rating scale for positive- and negative-reinforcement smoking: The Michigan Nicotine Reinforcement Questionnaire.
Authors: Pomerleau O.F. , Fagerström K.O. , Marks J.L. , Tate J.C. , Pomerleau C.S. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2003 Oct; 5(5), p. 711-8.
PMID: 14577987
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Smoking patterns and abstinence effects in smokers with no ADHD, childhood ADHD, and adult ADHD symptomatology.
Authors: Pomerleau C.S. , Downey K.K. , Snedecor S.M. , Mehringer A.M. , Marks J.L. , Pomerleau O.F. .
Source: Addictive Behaviors, 2003 Aug; 28(6), p. 1149-57.
PMID: 12834657
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Agreement between proband and parental self-report of smoking behavior and nicotine dependence.
Authors: Marks J.L. , Swan G.E. , Pomerleau C.S. , Pomerleau O.F. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2003 Aug; 5(4), p. 527-33.
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Patterns of inattentive and hyperactive symptomatology in cocaine-addicted and non-cocaine-addicted smokers diagnosed with adult attention deficit hyperactivity disorder.
Authors: Saules K.K. , Pomerleau C.S. , Schubiner H. .
Source: Journal Of Addictive Diseases, 2003; 22(2), p. 71-8.
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Estimating two-stage models for genetic influences on alcohol, tobacco or drug use initiation and dependence vulnerability in twin and family data.
Authors: Heath A.C. , Martin N.G. , Lynskey M.T. , Todorov A.A. , Madden P.A. .
Source: Twin Research : The Official Journal Of The International Society For Twin Studies, 2002 Apr; 5(2), p. 113-24.
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The Assessment of Hyperactivity and Attention (AHA): development and preliminary validation of a brief self-assessment of adult ADHD.
Authors: Mehringer A.M. , Downey K.K. , Schuh L.M. , Pomerleau C.S. , Snedecor S.M. , Schbiner H. .
Source: Journal Of Attention Disorders, 2002 Mar; 5(4), p. 223-31.
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An integrative approach for studying the etiology of alcoholism and other addictions.
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Who gets what symptom? Effects of psychiatric cofactors and nicotine dependence on patterns of smoking withdrawal symptomatology.
Authors: Pomerleau C.S. , Marks J.L. , Pomerleau O.F. .
Source: Nicotine & Tobacco Research : Official Journal Of The Society For Research On Nicotine And Tobacco, 2000 Aug; 2(3), p. 275-80.
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Introduction to the featured section: genetic research on smoking.
Authors: Pomerleau O.F. , Kardia S.L. .
Source: Health Psychology : Official Journal Of The Division Of Health Psychology, American Psychological Association, 1999 Jan; 18(1), p. 3-6.
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