The Yale-SCOR is bringing together leading basic and clinical science experts to establish an interdisciplinary, translational, cross-species program of research aimed at identifying novel therapeutics to address the critical health disparity that female smokers face. Tobacco use is the leading cause of preventable morbidity and mortality in the United States. Women, compared to men, have poorer rates of smoking cessation, exacerbated health risks, and FDA-approved medications for smoking cessation may not be as effective for women or have emerging limits due to side effects. However, few attempts have been made to develop gender-sensitive smoking cessation treatments. The considerable body of data suggesting that women are more likely to smoke to regulate negative affect and stress while men are more likely to smoke for the reinforcing properties of nicotine suggests an important direction in the development of a new approach to smoking cessation treatments. Using both preclinical and clinical strategies, our interdisciplinary team will probe te noradrenergic system's effects on stress-reactivity and nicotine reinforcement -hypothesizing that (a) different brain systems modulated by noradrenergic activity are activated by smoking in women and men, and (b) guanfacine (an alpha-2a noradrenergic agonist) can preferentially target these gender-sensitive systems to improve smoking cessation outcomes. Using a translational approach with an interdisciplinary team effort, we are proposing three projects that will have inter-related and shared goals, with each providing unique contributions to the development of gender-sensitive therapeutics. This new application will catalyze Yale's significant resources to support interdisciplinary and translational science in women's health to pursue extremely timely scientific findings that could represent a breakthrough in our understanding of treatments for a public health problem that affects millions daily.
Our specific aims and objectives of the Yale-SCOR are to:
AIM 1 : Evaluate the role of the noradrenergic system and its interactions with cholinergic and dopaminergic systems, in stress-induced smoking relapse and nicotine-based reinforcement, and use these findings to inform and expedite the development of gender-sensitive therapeutics for smoking cessation.
AIM 2 : Mentor junior investigators in conducting interdisciplinary translational research on tobacco use and women's health through training opportunities, including """"""""clerkships"""""""" with SCOR PIs, and pilot funding.
AIM 3 : Be a national resource to invigorate and galvanize the study of sex and gender differences in relation to smoking by providing expert consultation;supporting faculty training awards;mining national data on gender, smoking and health outcomes to inform health policy;and expanding our current program of local and national community outreach.

Public Health Relevance

Women compared to men, have poorer rates of smoking cessation and exacerbated health risks yet few attempts have been made to develop gender-sensitive smoking cessation treatments. This research will contribute to the public health by providing a neurobiologically-informed approach to the development of gender-sensitive therapeutics for smoking cessation, mentoring the next generation of interdisciplinary and translational researchers, and providing a national resource for women's health and tobacco use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
5P50DA033945-02
Application #
8501386
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Program Officer
Walton, Kevin
Project Start
2012-07-01
Project End
2017-05-31
Budget Start
2013-07-01
Budget End
2014-05-31
Support Year
2
Fiscal Year
2013
Total Cost
$1,170,462
Indirect Cost
$589,929
Name
Yale University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Verplaetse, Terril L; Weinberger, Andrea H; Ashare, Rebecca L et al. (2018) Pilot investigation of the effect of carvedilol on stress-precipitated smoking-lapse behavior. J Psychopharmacol 32:1003-1009
Verplaetse, Terril L; Moore, Kelly E; Pittman, Brian P et al. (2018) Intersection of e-cigarette use and gender on transitions in cigarette smoking status: Findings across waves 1 and 2 of the Population Assessment of Tobacco and Health (PATH) study. Nicotine Tob Res :
Moran-Santa Maria, Megan M; Vanderweyen, Davy C; Camp, Christopher C et al. (2018) Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study. Nicotine Tob Res 20:810-818
Mineur, Yann S; Cahuzac, Emma L; Mose, Tenna N et al. (2018) Interaction between noradrenergic and cholinergic signaling in amygdala regulates anxiety- and depression-related behaviors in mice. Neuropsychopharmacology 43:2118-2125
Han, MeiLan K; Arteaga-Solis, Emilio; Blenis, John et al. (2018) Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease. Am J Respir Crit Care Med 198:850-858
Verplaetse, Terril L; Moore, Kelly E; Pittman, Brian P et al. (2018) Intersection of stress and gender in association with transitions in past year DSM-5 substance use disorder diagnoses in the United States. Chronic Stress (Thousand Oaks) 2:
Oberleitner, Lindsay M S; Moore, Kelly E; Verplaetse, Terril et al. (2018) Developing a laboratory model of smoking lapse targeting stress and brief nicotine deprivation. Exp Clin Psychopharmacol 26:244-250
Mineur, Yann S; Mose, Tenna N; Blakeman, Sam et al. (2018) Hippocampal ?7 nicotinic ACh receptors contribute to modulation of depression-like behaviour in C57BL/6J mice. Br J Pharmacol 175:1903-1914
Roberts, Walter; Verplaetse, Terril L; Moore, Kelly E et al. (2018) A preliminary investigation into the effects of doxazosin on cognitive functioning in tobacco-deprived and -satiated smokers. Hum Psychopharmacol 33:e2660
Jung, Yonwoo; Lee, Angela M; McKee, Sherry A et al. (2017) Maternal smoking and autism spectrum disorder: meta-analysis with population smoking metrics as moderators. Sci Rep 7:4315

Showing the most recent 10 out of 85 publications