title: 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.
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.
authors.affiliation: Department of Neurology, University of Cincinnati, Cincinnati, OH 45267, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Carter
authors.forename: Jon
authors.initials: J
authors.lastname: Dickerson
authors.forename: Darryle D
authors.initials: DD
authors.lastname: Schoepp
authors.forename: Melinda
authors.initials: M
authors.lastname: Reilly
authors.forename: Nicole
authors.initials: N
authors.lastname: Herring
authors.forename: Jon
authors.initials: J
authors.lastname: Williams
authors.forename: Floyd R
authors.initials: FR
authors.lastname: Sallee
authors.forename: James W
authors.initials: JW
authors.lastname: Sharp
authors.forename: Frank R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D000596:Amino Acids / Q000008:administration & dosage*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000633:toxicity*; D005260:Female; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011618:Psychotic Disorders / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists* / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D013788:Thalamus / Q000187:drug effects / Q000293:injuries / Q000378:metabolism
chemical_list: D000596:Amino Acids; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018840:HSP70 Heat-Shock Proteins; C118218:LY 379268; D018094:Receptors, Metabotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C108822:metabotropic glutamate receptor 2; C102718:metabotropic glutamate receptor 3; D016291:Dizocilpine Maleate