2008 - 2009 Publications > Genetics of Opioid Addiction

Recent Findings

Molecular Genetics of Opiate Dependence

• Hawes et al Neuropsychopharmacology. 2008 Jul;33(8):1864-73 suggest that galanin normally attenuates behavioral and neurochemical effects of opiates; thus, galanin agonists may represent a new class of therapeutic targets for opiate addiction.
• Horvath et al J. Neurosci 2007 Dec 5;27(49):13371-5 reports decrease mRNA expression of DAT in the paranigral nucleus (PN), portions of the VTA, and striatum.  Significant reductions in NURR1 a transcription factor that regulates DAT expression was observed in the PN. In contrast, TH and synuclein were elevated in the PN.  Dysregulation of G proteins to MOR and KOR is also seen in the PN of heroin addicts.
• Bogulavsky et al J. Pharmacol. Exp. Ther. 2009 Feb;328(2):579-87 report that deletion of the Glur5 subunit of the kainite receptor blocks morphine tolerance without affecting without affecting nociceptive thresholds, morphine analgesia, disposition in CNS of morphine and its metabolite morphine-3-glucuronide or the acquisition of morphine conditioned place preference.
• Charlton et al Neuron. 2008 Apr 24;58(2):238-47 reports that targeted deletion of spinophilin, a dendritic scaffolding protein causes reduced sensitivity to the analgesic effects of morphine and early development of tolerance but a higher degree of physical dependence and increased sensitivity to the rewarding actions of the drug. At the cellular level, spinophilin associates with the mu opioid receptor (MOR) in striatum and modulates MOR signaling and endocytosis.
• Crombag et al Neuropsychopharmacology. 2008 Jun 4 report that deletion of narp, a neuronal IEG that associates with AMPA receptors, blocks extinction of morphine conditioned place preference.
• Reti et al Behav Neurosci. 2008 Aug;122(4):760-8 suggests that Narp modulates both acquisition and extinction of aversive responses to morphine withdrawal
• Glass et al Exp Neurol. 2008 Sep;213(1):57-70 report that Conditional deletion of the NMDA-NR1 receptor subunit gene in the central nucleus of the amygdala inhibits naloxone-induced conditioned place aversion in morphine-dependent mice without affecting somatic withdrawal symptoms.
• Levran et al Hum. Mol. Genet. 2008 Jul 15;17(14):2219-27 report that variants of p-glycoprotein ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence
• Nielsen et al Neuropsychopharmacology. 2008 Jul 23 reports increased OPRM1 DNA methylation in lymphocytes of methadone-maintained former heroin addicts.

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