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

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 103; no. 20; pp. 7883 - 7888
• Main Authors: Drakenberg, Katarina, Nikoshkov, Andrej, Horváth, Monika Cs, Fagergren, Pernilla, Gharibyan, Anna, Saarelainen, Kati, Rahman, Sadia, Nylander, Ingrid, Bakalkin, Georgy, Rajs, Jovan, Keller, Eva, Hurd, Yasmin L.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 16-05-2006
• Series: From the Cover
• Subjects: Adolescent; Adult; Autopsy; Biological Sciences; Caudate nucleus; Drug abuse; dynorphin; enkephalin; Female; Gene expression; Genetic Predisposition to Disease; Genotype; Genotypes; Heroin; Heroin dependence; Heroin Dependence - genetics; Humans; Male; MEDICIN; Medicin och hälsovetenskap; MEDICINE; Messenger RNA; Middle Aged; Morphine; mRNA; Neurology; Neuropeptides; Opioid analgesics; Opioid Peptides - genetics; Opioid Peptides - metabolism; Polymorphism, Genetic; Proprotein Convertase 2 - genetics; Proprotein Convertase 2 - metabolism; Putamen; Receptors, Opioid, mu - genetics; Receptors, Opioid, mu - metabolism; Ribonucleic acid; RNA; RNA, Messenger - metabolism; Toxicology; Visual Cortex - physiology; White People
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.0600871103

μ Opioid receptors are critical for heroin dependence, and A118G SNP of the μ opioid receptor gene (OPRM1) has been linked with heroin abuse. In our population of European Caucasians (n = 118), ≈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.