The main goal of this project is to examine sex differences in cocaine cessation and relapse through treatment with exogenous progesterone (PRO) compared to placebo, and to examine impulsivity as a moderating variable by the addition of atomoxetine (ATOM) to PRO. In females, both human and animal studies demonstrate a more rapid progression to dependence, poorer outcomes, and greater effect of cocaine;sex hormones likely play a prominent role (Hyman et.al., 2008, Tuchman, 2010). PRO is of interest because of its attenuation of subjective effects of cocaine (Sofuogu 2004) and craving (Specker 2010) as well as its potential impact on impulsivity. Impulsivity is clearly associated with risk for addiction. Atomoxetine s chosen because of the finding of improvement in impulsivity tasks in animals (Robinson, 2008). Here we will examine the interplay of PRO, impulsivity and sex differences in drug taking and cessation while examining effects of ATOM on impulsivity. Cocaine dependent + nicotine dependent females and males will be studied in a double blind randomized trial with three groups: PRO/Placebo, PRO+ATOM/Placebo, and Placebo/Placebo. Cocaine and nicotine dependence coexist and have many commonalities;hence we propose to study this population. The overall design parallels Project I and provides a unique opportunity to study both cocaine and nicotine and delineate sex differences.

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. PROJECT/PERFORIVIANCE SITE(S) (if additional space is needed, use Project/

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Specialized Center (P50)
Project #
1P50DA033942-01
Application #
8366482
Study Section
Special Emphasis Panel (ZRG1-EMNR-Q (50))
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$161,413
Indirect Cost
$51,771
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
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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) 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; 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
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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
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
Radke, Anna K; Gewirtz, Jonathan C; Carroll, Marilyn E (2015) Effects of age, but not sex, on elevated startle during withdrawal from acute morphine in adolescent and adult rats. Behav Pharmacol 26:485-8
Hinderaker, Katie; Allen, Alicia M; Tosun, Nicole et al. (2015) The effect of combination oral contraceptives on smoking-related symptomatology during short-term smoking abstinence. Addict Behav 41:148-51
Adanyeguh, Isaac M; Henry, Pierre-Gilles; Nguyen, Tra M et al. (2015) In vivo neurometabolic profiling in patients with spinocerebellar ataxia types 1, 2, 3, and 7. Mov Disord 30:662-70

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