Mu Opioid Receptor A118G Polymorphism in Association with Striatal Opioid Neuropeptide Gene Expression in Heroin Abusers

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2006 May 10

PMID 16682632

Citations 63

Authors

Katarina Drakenberg

Andrej Nikoshkov

Monika Cs Horvath

Pernilla Fagergren

Anna Gharibyan

Kati Saarelainen

Sadia Rahman

Ingrid Nylander

Georgy Bakalkin

Jovan Rajs

Eva Keller

Yasmin L Hurd

Affiliations

Soon will be listed here.

Abstract

Mu opioid receptors are critical for heroin dependence, and A118G SNP of the mu opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), approximately 90% of 118G allelic carriers were heroin users. Postmortem brain analyses showed the OPRM1 genotype associated with transcription, translation, and processing of the human striatal opioid neuropeptide system. Whereas down-regulation of preproenkephalin and preprodynorphin genes was evident in all heroin users, the effects were exaggerated in 118G subjects and were most prominent for preproenkephalin in the nucleus accumbens shell. Reduced opioid neuropeptide transcription was accompanied by increased dynorphin and enkephalin peptide concentrations exclusively in 118G heroin subjects, suggesting that the peptide processing is associated with the OPRM1 genotype. Abnormal gene expression related to peptide convertase and ubiquitin/proteosome regulation was also evident in heroin users. Taken together, alterations in opioid neuropeptide systems might underlie enhanced opiate abuse vulnerability apparent in 118G individuals.

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