: The goal of this SCOR is to take an interdisciplinary approach to studying an emerging and potentially important interaction between sex differences, hormonal status (e.g., progesterone - PRO), impulsivity, and drug-motivated behavior that could have important consequences for reducing two devastating forms of drug abuse, cigarette smoking and cocaine abuse. The central hypothesis is that reducing impulsivity will reduce drug-seeking behavior. Progesterone reduces impulsivity, and combined with drugs that have similar effects (e.g., atomoxetine - ATO), significant reductions in nicotine and cocaine abuse may be achieved. PRO will also be tested in combination with drugs that show some effect for nicotine dependence, varenicline (VAR) in the animal project. Based on a growing literature on sex differences in drug abuse, there may be sex differences in the effect of single and combined treatments. The following are the Specific Aims of the SCOR: 1. Investigate sex differences in the effect of exogenous PRO compared to placebo on impulsivity and smoking cessation in clinical Project 1. 2. To study sex differences in the effect of exogenous PRO vs. placebo in combination with ATO vs. placebo on impulsivity and relapse to cocaine abuse in clinical Project 2. 3. To examine sex differences in an animal model of nicotine and cocaine relapse and impulsivity for nicotine or cocaine in rats treated with PRO alone and in combination with ATO and VAR. Another goal is to study endogenous PRO effects on nicotine or cocaine self-administration in pregnant rats during gestation (high PRO) and lactation (low PRO) compared with males and no pregnant females. This SCOR allows for an interdisciplinary and translational approach to accomplishing these aims. It also offers economic efficiency, an opportunity to exchange ideas and approaches with others who are involved with the SCOR.

Public Health Relevance

Despite much effort, there are not yet highly effective approved medications for the direct treatment of cocaine and nicotine dependence. This SCOR will carry out interdisciplinary and translational investigations to identify pharmacological interventions targeting behaviors impaired in nicotine and cocaine dependent subjects to enhance the effectiveness of existing behavioral treatments for addiction.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
1P50DA033942-01
Application #
8343994
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Program Officer
Kautz, Mary A
Project Start
2012-08-01
Project End
2017-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$1,120,279
Indirect Cost
$372,232
Name
University of Minnesota Twin Cities
Department
Psychiatry
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Allen, Alicia M; McRae-Clark, Aimee L; Carlson, Samantha et al. (2016) Determining menstrual phase in human biobehavioral research: A review with recommendations. Exp Clin Psychopharmacol 24:1-11
Swalve, Natashia; Smethells, John R; Carroll, Marilyn E (2016) Sex differences in the acquisition and maintenance of cocaine and nicotine self-administration in rats. Psychopharmacology (Berl) 233:1005-13
Swalve, Natashia; Smethells, John R; Zlebnik, Natalie E et al. (2016) Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine. Pharmacol Biochem Behav 145:17-23
Carroll, Marilyn E; Lynch, Wendy J (2016) How to study sex differences in addiction using animal models. Addict Biol 21:1007-29
Swalve, Natashia; Smethells, John R; Carroll, Marilyn E (2016) Progesterone attenuates impulsive action in a Go/No-Go task for sucrose pellets in female and male rats. Horm Behav 85:43-7
Smethells, John R; Swalve, Natashia L; Eberly, Lynn E et al. (2016) Sex differences in the reduction of impulsive choice (delay discounting) for cocaine in rats with atomoxetine and progesterone. Psychopharmacology (Berl) 233:2999-3008
Smethells, J R; Zlebnik, N E; Miller, D K et al. (2016) Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running. Drug Alcohol Depend 167:163-8
Swalve, Natashia; Smethells, John R; Carroll, Marilyn E (2016) Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline. Behav Brain Res 308:46-52
Lawless, Michael H; Harrison, Katherine A; Grandits, Gregory A et al. (2015) Perceived stress and smoking-related behaviors and symptomatology in male and female smokers. Addict Behav 51:80-3
Weinberger, Andrea H; Smith, Philip H; Allen, Sharon S et al. (2015) Systematic and meta-analytic review of research examining the impact of menstrual cycle phase and ovarian hormones on smoking and cessation. Nicotine Tob Res 17:407-21

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