Abstract

The Mu opioid receptor (MOR) is responsible for many of the major effects of morphine and related drugs, and the interaction between MOR and other cell signaling molecules is the focus of this project. It is hypothesized that MOR interacting proteins, MORIPs, are important for regulation of the MOR, especially as regards opioid dependence and addiction. In order to better understand the role of MORIPs in opioid pharmacology and dependence, the effects of acute and opioid treatment on expression of known MORIPs in regional brain areas of B6 mice will be assessed using a series of agonists with different MOR binding properties. A novel MORIP, GPR177, will be assessed through the study of GPR177 transgenic mice. Mice which underexpress and overexpress the GPR177 molecule will be studied biochemically (MORIP and MOR gene expression) and behaviorally (opioid dependence phenotypes and phenotypes related to general opioid pharmacology) using both acute and chronic opioid treatment with morphine, etorphine and buprenorphine. We will also examine the effects of naloxone-precipated withdrawal from chronic morphine treatment in this model. In addition we will study cellular phenotypes related to chronic opioid treatment including measures of dendritic arborization and neurogenesis. Overall studies will shed light on the role of MORIPs, and GPR177 in particular, in the effects of opioids related to opioid dependence

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Exploratory Grants (P20)
Project #
5P20DA025995-03
Application #
8101351
Study Section
Special Emphasis Panel (ZDA1)
Project Start
Project End
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
3
Fiscal Year
2010
Total Cost
$289,201
Indirect Cost

  Institution

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

  Publications

Tacelosky, Diana M; Alexander, Danielle N; Morse, Megan et al. (2015) Low expression of D2R and Wntless correlates with high motivation for heroin. Behav Neurosci 129:744-55
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
Crist, Richard C; Berrettini, Wade H (2014) Pharmacogenetics of OPRM1. Pharmacol Biochem Behav 123:25-33
Ebersole, Brittany; Petko, Jessica; Levenson, Robert (2014) Bioorthogonal click chemistry to assay mu-opioid receptor palmitoylation using 15-hexadecynoic acid and immunoprecipitation. Anal Biochem 451:25-7
Doyle, G A; Schwebel, C L; Ruiz, S E et al. (2014) Analysis of candidate genes for morphine preference quantitative trait locus Mop2. Neuroscience 277:403-16
Jaremko, Kellie M; Thompson Jr, Nicholas L; Reyes, Beverly A S et al. (2014) Morphine-induced trafficking of a mu-opioid receptor interacting protein in rat locus coeruleus neurons. Prog Neuropsychopharmacol Biol Psychiatry 50:53-65
Petko, Jessica; Justice-Bitner, Stephanie; Jin, Jay et al. (2013) MOR is not enough: identification of novel mu-opioid receptor interacting proteins using traditional and modified membrane yeast two-hybrid screens. PLoS One 8:e67608
Clarke, Toni-Kim; Bloch, Paul J; Ambrose-Lanci, Lisa M et al. (2013) Further evidence for association of polymorphisms in the CNR1 gene with cocaine addiction: confirmation in an independent sample and meta-analysis. Addict Biol 18:702-8
Clarke, Toni-Kim; Crist, Richard C; Kampman, Kyle M et al. (2013) Low frequency genetic variants in the ?-opioid receptor (OPRM1) affect risk for addiction to heroin and cocaine. Neurosci Lett 542:71-5

Showing the most recent 10 out of 23 publications