Cellular distribution of AMPA receptor subunits and mGlu5 following acute and repeated administration of morphine or methamphetamine

Authors

  • Amy A. Herrold,

    1. Laboratory of Origin, Department of Pharmacology, Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, Illinois, USA
    2. Neuroscience Graduate Program, Stritch School of Medicine, Loyola University Chicago, Maywood, Illinois, USA
    Current affiliation:
    1. Center for Management of Complex Chronic Care, Edward Hines Jr., VA Hospital, Hines, Illinois, USA
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  • Amanda L. Persons,

    1. Laboratory of Origin, Department of Pharmacology, Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, Illinois, USA
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    • Previously published as A. L. Mickiewicz.
  • T. Celeste Napier

    Corresponding author
    • Laboratory of Origin, Department of Pharmacology, Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, Illinois, USA
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Address correspondence and reprint requests to Dr. T. Celeste Napier, Center for Compulsive Behavior and Addiction, Department of Pharmacology, Rush University Medical Center, Cohn Research Building, Suite 424, 1735 W. Harrison St., Chicago, IL 60612, USA. E-mail: celeste_napier@rush.edu

Abstract

Ionotropic AMPA receptors (AMPAR) and metabotropic glutamate group I subtype 5 receptors (mGlu5) mediate neuronal and behavioral effects of abused drugs. mGlu5 stimulation increases expression of striatal-enriched tyrosine phosphatase isoform 61 (STEP61) which internalizes AMPARs. We determined the rat brain profile of these proteins using two different classes of abused drugs, opiates, and stimulants. STEP61 levels, and cellular distribution/expression of AMPAR subunits (GluA1, GluA2) and mGlu5, were evaluated via a protein cross-linking assay in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and ventral pallidum (VP) harvested 1 day after acute, or fourteen days after repeated morphine (8 mg/kg) or methamphetamine (1 mg/kg) (treatments producing behavioral sensitization). Acute morphine decreased GluA1 and GluA2 surface expression in mPFC and GluA1 in NAc. Fourteen days after repeated morphine or methamphetamine, mGlu5 surface expression increased in VP. In mPFC, mGlu5 were unaltered; however, after methamphetamine, STEP61 levels decreased and GluA2 surface expression increased. Pre-treatment with a mGlu5-selective negative allosteric modulator, blocked methamphetamine-induced behavioral sensitization and changes in mPFC GluA2 and STEP61. These data reveal (i) region-specific distinctions in glutamate receptor trafficking between acute and repeated treatments of morphine and methamphetamine, and (ii) that mGlu5 is necessary for methamphetamine-induced alterations in mPFC GluA2 and STEP61.

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