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Cellular distribution of AMPA receptor subunits and mGlu5 following acute and repeated administration of morphine or methamphetamine
Author(s) -
Herrold Amy A.,
Persons Amanda L.,
Napier T. Celeste
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12323
Subject(s) - methamphetamine , ampa receptor , pharmacology , morphine , chemistry , distribution (mathematics) , receptor , neuroscience , glutamate receptor , medicine , biology , biochemistry , mathematical analysis , mathematics
Ionotropic AMPA receptors (AMPAR) and metabotropic glutamate group I subtype 5 receptors (mGlu5) mediate neuronal and behavioral effects of abused drugs. mG lu5 stimulation increases expression of striatal‐enriched tyrosine phosphatase isoform 61 (STEP 61 ) which internalizes AMPARs. We determined the rat brain profile of these proteins using two different classes of abused drugs, opiates, and stimulants. STEP 61 levels, and cellular distribution/expression of AMPAR subunits (GluA1, GluA2) and mG lu5, 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, mG lu5 surface expression increased in VP. In mPFC , mG lu5 were unaltered; however, after methamphetamine, STEP 61 levels decreased and GluA2 surface expression increased. Pre‐treatment with a mG lu5‐selective negative allosteric modulator, blocked methamphetamine‐induced behavioral sensitization and changes in mPFC GluA2 and STEP 61 . These data reveal (i) region‐specific distinctions in glutamate receptor trafficking between acute and repeated treatments of morphine and methamphetamine, and (ii) that mG lu5 is necessary for methamphetamine‐induced alterations in mPFC GluA2 and STEP 61 .