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Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in r

Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in r

  1. Anonymous
    BMC Neuroscience 2008, 9:39 doi:10.1186/1471-2202-9-39
    Anna MS Kindlundh-Högberg, Anna Blomqvist, Rana Malki and Helgi B Schiöth

    Abstract
    Background: Many studies have focused on the implication of the serotonin and dopamine
    systems in neuroadaptive responses to the recreational drug 3,4-methylenedioxy-metamphetamine
    (MDMA). Less attention has been given to the major excitatory neurotransmitter glutamate known
    to be implicated in schizophrenia and drug addiction. The aim of the present study was to
    investigate the effect of repeated intermittent MDMA administration upon gene-transcript
    expression of the glutamate transporters (EAAT1, EAAT2-1, EAAT2-2), the glutamate receptor
    subunits of AMPA (GluR1, GluR2, GluR3), the glutamate receptor subunits of NMDA (NR1, NR2A
    and NR2B), as well as metabotropic glutamate receptors (mGluR1, mGluR2, mGluR3, mGluR5) in
    six different brain regions. Adolescent male Sprague Dawley rats received MDMA at the doses of
    3 × 1 and 3 × 5 mg/kg/day, or 3× vehicle 3 hours apart, every 7th day for 4 weeks. The genetranscript
    levels were assessed using real-time PCR validated with a range of housekeeping genes.
    Results: The findings showed pronounced enhancements in gene-transcript expression of GluR2,
    mGluR1, mGluR5, NR1, NR2A, NR2B, EAAT1, and EAAT2-2 in the cortex at bregma +1.6. In the
    caudate putamen, mRNA levels of GluR3, NR2A, and NR2B receptor subunits were significantly
    increased. In contrast, the gene-transcript expression of GluR1 was reduced in the hippocampus.
    In the hypothalamus, there was a significant increase of GluR1, GluR3, mGluR1, and mGluR3 genetranscript
    expressions.
    Conclusion: Repeated intermittent MDMA administration induces neuroadaptive changes in
    gene-transcript expressions of glutamatergic NMDA and AMPA receptor subunits, metabotropic
    receptors and transporters in regions of the brain regulating reward-related associative learning,
    cognition, and memory and neuro-endocrine functions.