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

• Published in: Journal of neurochemistry Vol. 126; no. 4; pp. 503 - 517
• Main Authors: Herrold, Amy A., Persons, Amanda L., Napier, T. Celeste
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01-08-2013
• Subjects: Allosteric properties; Analgesics, Opioid - pharmacology; Animals; Blotting, Western; Brain Chemistry - drug effects; Central Nervous System Stimulants - pharmacology; Drug therapy; Globus Pallidus - drug effects; Globus Pallidus - metabolism; GluA1; GluA2; Male; metabotropic glutamatergic receptors; Methamphetamine - pharmacology; Morphine - pharmacology; MTEP; Neurochemistry; Neurosciences; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Protein Tyrosine Phosphatases, Non-Receptor - metabolism; Rats; Rats, Sprague-Dawley; Receptor, Metabotropic Glutamate 5; Receptors, AMPA - metabolism; Receptors, Metabotropic Glutamate - metabolism; sensitization; STEP61; Substance Withdrawal Syndrome - metabolism; metabotropic glutamatergic receptors; GluA2; GluA1; sensitization; STEP61; MTEP
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/jnc.12323

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.
Chronic methamphetamine results in glutamate release and synaptic plasticity, likely involving AMPA receptors. Metabotropic glutamate receptor group 1 subtype 5 (mGlu5) activates striatal‐enriched tyrosine phosphatase isoform 61 (STEP61) to internalize AMPARs. We reveal that repeated methamphetamine increased cell surface AMPAR subunits and decreased STEP61 levels in rat cortex; this change was not seen after mGlu5 antagonist treatment.