Ethanol self-administration modulation of NMDA receptor subunit and related synaptic protein mRNA expression in prefrontal cortical fields in cynomolgus monkeys

Glen Acosta, Wendy Hasenkamp, James B. Daunais, David P. Friedman, Kathleen (Kathy) Grant, Scott E. Hemby

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Background: Functional impairment of the orbital and medial prefrontal cortex underlies deficits in executive control that characterize addictive disorders, including alcohol addiction. Previous studies indicate that alcohol alters glutamate neurotransmission and one substrate of these effects may be through the reconfiguration of the subunits constituting ionotropic glutamate receptor (iGluR) complexes. Glutamatergic transmission is integral to cortico-cortical and cortico-subcortical communication, and alcohol-induced changes in the abundance of the receptor subunits and/or their splice variants may result in critical functional impairments of prefrontal cortex in the alcohol-addicted state. Methods and results: The effects of chronic ethanol self-administration on glutamate receptor ionotropic NMDA (GRIN), as well as GRIN1 splice variant mRNA expression was studied in the orbitofrontal cortex (OFC; Area 13), dorsolateral prefrontal cortex (DLPFC; Area 46) and anterior cingulate cortex (ACC; Area 24) of male cynomolgus monkeys. Chronic ethanol self-administration resulted in significant changes in the expression of NMDA subunit mRNA expression in the DLPFC and OFC, but not the ACC. In DLPFC, the overall expression of NMDA subunits was significantly decreased in ethanol treated monkeys. Slight but significant changes were observed for synaptic associated protein 102 kD (SAP102) and neuronal nitric oxide synthase (nNOS) mRNAs. In OFC, the NMDAR1 variant GRIN1-1 was reduced while GRIN1-2 was increased. Furthermore, no significant changes in GFAP protein levels were observed in either the DLPFC or OFC. Conclusion: Results from these studies provide the first demonstration of posttranscriptional regulation of iGluR subunits in the primate brain following long-term ethanol self-administration. Furthermore, changes in these transcripts do not appear to reflect changes in glial activation or loss. Further studies examining the expression and cellular localization of subunit proteins and receptor pharmacology would shed more light on the findings reported here.

    Original languageEnglish (US)
    Pages (from-to)144-154
    Number of pages11
    JournalBrain Research
    Volume1318
    DOIs
    StatePublished - Mar 8 2010

    Fingerprint

    Self Administration
    Macaca fascicularis
    Prefrontal Cortex
    N-Methyl-D-Aspartate Receptors
    Ionotropic Glutamate Receptors
    Ethanol
    N-Methylaspartate
    Messenger RNA
    Alcohols
    Proteins
    Nitric Oxide Synthase Type I
    Gyrus Cinguli
    Executive Function
    Protein Subunits
    Synaptic Transmission
    Neuroglia
    Primates
    Alcoholism
    Haplorhini
    Glutamic Acid

    Keywords

    • Ethanol
    • Glutamate
    • Messenger RNA
    • Prefrontal Cortex
    • Primate
    • qPCR

    ASJC Scopus subject areas

    • Neuroscience(all)
    • Clinical Neurology
    • Developmental Biology
    • Molecular Biology

    Cite this

    Ethanol self-administration modulation of NMDA receptor subunit and related synaptic protein mRNA expression in prefrontal cortical fields in cynomolgus monkeys. / Acosta, Glen; Hasenkamp, Wendy; Daunais, James B.; Friedman, David P.; Grant, Kathleen (Kathy); Hemby, Scott E.

    In: Brain Research, Vol. 1318, 08.03.2010, p. 144-154.

    Research output: Contribution to journalArticle

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    AU - Daunais, James B.

    AU - Friedman, David P.

    AU - Grant, Kathleen (Kathy)

    AU - Hemby, Scott E.

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