This proposal is the second revision of an application originally submitted in February 2003 and resubmitted in November 2003. The goal of the proposed Mentored Patient-Oriented Research Career Development Award is to build upon the previous training and experience of Michael Kotlyar, PharmD, a tenure track assistant professor in Experimental and Clinical Pharmacology and Psychiatry. Via the mentorship, training and research proposed in this application, it is expected that Dr. Kotlyar can develop into an independent, funded investigator. To further develop skills in clinical trial design, biostatistics and ethics, Dr. Kotlyar will enroll in a formal program of study leading to a Master's degree in the Clinical Research Masters Program at the University of Minnesota. Dr. Dorothy Hatsukami, PhD, the director of the Tobacco Use Research Center will serve as Dr. Kotlyar's mentor. The research will assess the effect of paroxetine on the physiological response (blood pressure, heart rate and plasma catecholamine concentrations) and psychological discomfort during laboratory-administered mental stress tasks, administered immediately after smoking a cigarette. The research will be conducted in the NIH funded General Clinical Research Center (GCRC). We hypothesize that relative to placebo; paroxetine will decrease physiological response and reduce perceived psychological discomfort during mental stress tasks. The rationale for this research is that smokers often report smoking in response to stressful situations. Smoking and stress each result physiologically in an increase in sympathetic activity. When smoking is combined with stress, these effects are additive as assessed by measures such as increases in heart rate and blood pressure. Although high reactivity to stress is known to be detrimental to cardiovascular health, there is currently no data assessing the effect of antidepressants on the physiological response to stress in smokers or during the acute smoking period. The training and mentored research project combined with the guidance provided by an interdisciplinary advisory group should well prepare the candidate for a career as an independent, successful patient-oriented researcher.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Human Development Research Subcommittee (NIDA)
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Oversby, Steven
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University of Minnesota Twin Cities
Schools of Pharmacy
United States
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Kotlyar, Michael; Thuras, Paul; Hatsukami, Dorothy K et al. (2017) Sex differences in physiological response to the combination of stress and smoking. Int J Psychophysiol 118:27-31
Kotlyar, Michael; al'Absi, Mustafa; Thuras, Paul et al. (2013) Effect of paroxetine on physiological response to stress and smoking. Psychosom Med 75:236-43
Kotlyar, Michael; Drone, David; Thuras, Paul et al. (2011) Effect of stress and bupropion on craving, withdrawal symptoms, and mood in smokers. Nicotine Tob Res 13:492-7
Kotlyar, Michael; Hertsgaard, Louise A; Lindgren, Bruce R et al. (2011) Effect of oral snus and medicinal nicotine in smokers on toxicant exposure and withdrawal symptoms: a feasibility study. Cancer Epidemiol Biomarkers Prev 20:91-100
Kotlyar, Michael; al'Absi, Mustafa; Brauer, Lisa H et al. (2008) Naltrexone effect on physiological and subjective response to a cold pressor task. Biol Psychol 77:233-6
Kotlyar, Michael; Donahue, Christopher; Thuras, Paul et al. (2008) Physiological response to a speech stressor presented in a virtual reality environment. Psychophysiology 45:1034-7
Von Ruden, Abby E; Adson, David E; Kotlyar, Michael (2008) Effect of selective serotonin reuptake inhibitors on cardiovascular morbidity and mortality. J Cardiovasc Pharmacol Ther 13:32-40
Kotlyar, Michael; Mendoza-Baumgart, M Irene; Li, Zhong-ze et al. (2007) Nicotine pharmacokinetics and subjective effects of three potential reduced exposure products, moist snuff and nicotine lozenge. Tob Control 16:138-42
Kotlyar, Michael; Brauer, Lisa H; al'absi, Mustafa et al. (2006) Effect of bupropion on physiological measures of stress in smokers during nicotine withdrawal. Pharmacol Biochem Behav 83:370-9