This is a resubmission of a NIDA K08 Mentored Clinical Scientist Award. My career objective is to establish myself as independent investigator with a strong program of preclinical research focusing on the neurobiology of nicotine dependence and major depression. The application proposes a comprehensive, five-year program of supervised training and research with Raymond Niaura, Ph.D., and Lawrence H. Price, M.D., at Brown Medical School, and Marina Picciotto, Ph.D., and Tony P. George, M.D. at Yale School of Medicine. This multidisciplinary team will provide close guidance in a training plan comprised of structured didactics, seminars, and coursework in the Brown Brain Sciences Program and in the Department of Neuroscience at Yale University. The focus of the Research Plan is to characterize the neurobehavioral mechanisms that regulate cigarette cravings and smoking behavior among nicotine dependent individuals with and without vulnerability to major depression. In two double-blind, placebo-controlled challenge studies, acute tryptophan depletion (ATD) and alpha-methyl-para-tyrosine (AMPT) will be used to examine the effects of serotonin and dopamine depletion, respectively, on cravings and smoking topography.
The specific aims are: (1) To examine the role of serotonin and dopamine in regulating cigarette cravings and smoking topography in depression vulnerable smokers; (2) To determine the relative effects of ATD and AMPT administration on individual differences in (obsessive craving, reward craving) and smoking topography; (3) To determine whether any changes in cue-induced cravings in response to ATD or AMPT administration correspond to changes in smoking topography; and (4) To explore whether associations among craving-related measures (e.g., obsessive and reward craving), smoking (e.g., topography, blood nicotine levels), and diagnostic group are mediated by changes in mood. Results of this research will increase understanding of the associations among serotonin and dopamine function, cue-induced cravings and vulnerability to major depression, and may have implications for tailoring pharmacological treatments to nicotine craving profiles.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08DA017145-06
Application #
7459020
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Hoffman, Allison
Project Start
2004-09-30
Project End
2010-06-30
Budget Start
2008-07-01
Budget End
2010-06-30
Support Year
6
Fiscal Year
2008
Total Cost
$129,606
Indirect Cost
Name
Northwestern University at Chicago
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Hitsman, Brian; Papandonatos, George D; McChargue, Dennis E et al. (2013) Past major depression and smoking cessation outcome: a systematic review and meta-analysis update. Addiction 108:294-306
Hitsman, Brian; Hogarth, Lee; Tseng, Li-Jung et al. (2013) Dissociable effect of acute varenicline on tonic versus cue-provoked craving in non-treatment-motivated heavy smokers. Drug Alcohol Depend 130:135-41
Hitsman, Brian; Buka, Stephen L; Veluz-Wilkins, Anna K et al. (2011) Accuracy of a brief screening scale for lifetime major depression in cigarette smokers. Psychol Addict Behav 25:559-64
Hitsman, Brian; Shen, Biing-Jiun; Cohen, Ronald A et al. (2010) Measuring smoking-related preoccupation and compulsive drive: evaluation of the obsessive compulsive smoking scale. Psychopharmacology (Berl) 211:377-87
Hitsman, Brian; Moss, Taryn G; Montoya, Ivan D et al. (2009) Treatment of tobacco dependence in mental health and addictive disorders. Can J Psychiatry 54:368-78
Pagoto, Sherry L; Spring, Bonnie; McChargue, Dennis et al. (2009) Acute tryptophan depletion and sweet food consumption by overweight adults. Eat Behav 10:36-41
Weinberger, Andrea H; Hitsman, Brian; Papandonatos, George D et al. (2009) Predictors of abstinence and changes in psychiatric symptoms in a pooled sample of smokers with schizophrenia receiving combination pharmacotherapy and behavioral therapy for smoking cessation. J Clin Psychopharmacol 29:601-3
Gilman, Stephen E; Breslau, Joshua; Subramanian, S V et al. (2008) Social factors, psychopathology, and maternal smoking during pregnancy. Am J Public Health 98:448-53
Ziedonis, Douglas; Hitsman, Brian; Beckham, Jean C et al. (2008) Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report. Nicotine Tob Res 10:1691-715
Hitsman, Brian; MacKillop, James; Lingford-Hughes, Anne et al. (2008) Effects of acute tyrosine/phenylalanine depletion on the selective processing of smoking-related cues and the relative value of cigarettes in smokers. Psychopharmacology (Berl) 196:611-21

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