Abstract

Opioid dependence (OD) is a common, chronic, relapsing addiction with a substantial genetic component. Central to the neurobiology of OD is the mu opioid receptor (MOR), through which most of the rewarding effects of opioids are mediated. The goal of this project is to enhance our understanding of MOR in OD through linkage disequilibrium (LD) genetics studies of OD, using novel candidate genes, MOR interacting proteins (MORIPs). MOR exists as a complex with multiple binding partners (MORIPs) which mediate the signal transduction process, as well as receptor trafficking and desensitization. Relatively few MORIPs are known. Using existing MORIPs as well as novel ones identified through an independent collaboration, we will conduct a case-control association analysis of these known MORIPs and newly-defined MORIPs. We have assembled a set of DNA samples and clinical information from ~ 1500 OD individuals, whose data and biopecimens are in a central NIDA repository. In addition, we have access to ~ 4500 control DNA samples and clinical information from an NIMH repository. Using these resources, MORIP genes will be assessed for roles in genetic susceptibility to OD. Through this project, our understanding of the role of MOR in OD will be enhanced, opening new avenues for treatment of this common and severe addiction.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Comprehensive Center (P60)
Project #
5P60DA005186-25
Application #
8284405
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2012-06-30
Support Year
25
Fiscal Year
2011
Total Cost
$154,780
Indirect Cost

  Institution

Name
University of Pennsylvania
Department
Type
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104

  Publications

Franklin, Teresa R; Jagannathan, Kanchana; Hager, Nathan et al. (2018) Brain substrates of early (4h) cigarette abstinence: Identification of treatment targets. Drug Alcohol Depend 182:78-85
Wetherill, Reagan R; Jagannathan, Kanchana; Hager, Nathan et al. (2016) Influence of menstrual cycle phase on resting-state functional connectivity in naturally cycling, cigarette-dependent women. Biol Sex Differ 7:24
Woody, George E; Krupitsky, Evgeny; Zvartau, Edwin (2016) Antagonist Models for Relapse Prevention and Reducing HIV Risk. J Neuroimmune Pharmacol 11:401-7
Van Horn, Deborah H A; Drapkin, Michelle; Lynch, Kevin G et al. (2015) Treatment choices and subsequent attendance by substance-dependent patients who disengage from intensive outpatient treatment. Addict Res Theory 23:391-403
Franklin, Teresa R; Jagannathan, Kanchana; Wetherill, Reagan R et al. (2015) Influence of menstrual cycle phase on neural and craving responses to appetitive smoking cues in naturally cycling females. Nicotine Tob Res 17:390-7
Kampman, Kyle M; Lynch, Kevin G; Pettinati, Helen M et al. (2015) A double blind, placebo controlled trial of modafinil for the treatment of cocaine dependence without co-morbid alcohol dependence. Drug Alcohol Depend 155:105-10
Goldman, Marina; Ehrman, Ronald N; Suh, Jesse J et al. (2015) Brief report: ""spiders-No, puppies-Go"", introducing a novel Go NoGo task tested in inner city adolescents at risk for poor impulse control. J Adolesc 38:45-8
McKay, James R; Drapkin, Michelle L; Van Horn, Deborah H A et al. (2015) Effect of patient choice in an adaptive sequential randomization trial of treatment for alcohol and cocaine dependence. J Consult Clin Psychol 83:1021-32
Clarke, T-K; Crist, R C; Ang, A et al. (2014) Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females. Pharmacogenomics J 14:303-8
Clarke, Toni-Kim; Weiss, Amy R D; Ferarro, Thomas N et al. (2014) The dopamine receptor D2 (DRD2) SNP rs1076560 is associated with opioid addiction. Ann Hum Genet 78:33-9

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