Cellular distribution of AMPA receptor subunits and mGlu5 following acute and repeated administration of morphine or methamphetamine. (18th June 2013)

• Record Type: Journal Article
• Authors: Herrold, Amy A.; Persons, Amanda L.; Napier, T. Celeste
• Is Part Of: Journal of neurochemistry. Volume 126:Number 4(2013:Aug.)
• Page Start: 503
• Page End: 517
• Publication Date: 2013-06-18
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12323
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" id="jnc12323-abs-0001"> <title>Abstract</title> <p>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 (STEP<sub>61</sub>) which internalizes AMPARs. We determined the rat brain profile of these proteins using two different classes of abused drugs, opiates, and stimulants. STEP<sub>61</sub> levels, and cellular distribution/expression of AMPAR subunits (GluA1, GluA2) and mGlu5, were evaluated <italic>via</italic> 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, STEP<sub>61</sub> 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 STEP<sub>61</sub>. 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 STEP<sub>61</sub>.</p> </abstract>