Abstract

The general aim of the program is to identify changes in the opioid peptide systems that are characteristic of opiate (heroin) dependence. The five- year program described here is concentrated on one of the three opioid peptide genes, prodynorphin. Pre-clinical evidence suggests that dynorphins are involved in opiate tolerance, dependence and withdrawal. Studies will be conducted in two general phases: 1. pre-clinical phase in which we will continue our studies of the mechanisms of tolerance and dependence using animal models and tissues and/or isolated cells of human origin and 2. clinical phase in which we will apply knowledge obtained in the pre- clinical phase to observe and measure indices of dynorphin activity during specific stages of the human addiction cycle and during electrostimulation procedures that have been reported to increase endogenous opioid activity. Naturally, as in any long-range proposal, the studies performed in years three to five may be different depending on findings in the earlier years.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Comprehensive Center (P60)
Project #
2P60DA005186-11
Application #
6237875
Study Section
Project Start
1997-09-30
Project End
1998-06-30
Budget Start
1996-10-01
Budget End
1997-09-30
Support Year
11
Fiscal Year
1997
Total Cost
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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