The mGlu2/3 receptor agonist LY379268 injected into cortex or thalamus decreases neuronal injury in retrosplenial cortex produced by NMDA receptor antagonist MK-801: Possible implications for psychosis

Kevin Carter, Jon Dickerson, Darryle D. Schoepp, Melinda Reilly, Nicole Herring, Jon Williams, Floyd R. Sallee, James W. Sharp, Frank R Sharp

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The non-competitive NMDA receptor antagonists, including PCP (phencyclidine), ketamine, and MK-801 (dizocilpine) produce psychosis in humans and injure neurons in retrosplenial cortex in adult rodent brain. This study examined the effects of the metabotropic mGlu2/3 agonist LY379268 and antagonist LY341495 on cortical injury produced by systemic MK-801 (1 mg/kg i.p.) in adult female rats. Systemic injections of mGlu2/3 agonist LY379268, but not mGlu2/3 antagonist LY341495, decreased the injury in the retrosplenial cortex produced by systemic MK-801 as assessed by Hsp70 induction. Bilateral injections of LY379268, but not vehicle, into retrosplenial cortex or bilateral injections of LY379268 into anterior thalamus also decreased the injury in retrosplenial cortex produced by systemic MK-801. The data show that bilateral activation of mGlu2/3 glutamate receptors in cortex or anterior thalamus decreases the neuronal injury in retrosplenial cortex produced by systemic MK-801. Because antipsychotic medications decrease cortical injury produced by NMDA antagonists in rodents and decrease psychosis in humans, mGlu2/3 agonists that decrease cortical injury produced by NMDA antagonists in rodents might be evaluated for decreasing psychosis in people.

Original languageEnglish (US)
Pages (from-to)1135-1145
Number of pages11
JournalNeuropharmacology
Volume47
Issue number8
DOIs
StatePublished - Dec 2004

Keywords

  • G-protein coupled receptors
  • Glutamate receptors
  • Ketamine
  • Metabotropic glutamate receptors
  • NMDA receptors
  • Phencyclidine
  • Psychomimetics
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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