Interaction of blockers of ionotropic NMDA receptors and metabotropic glutamate receptors in a working memory test in rats.

Neuroscience and Behavioral Physiology
Y A NovitskayaA Y Bespalov

Abstract

Glutamate, the main excitatory neurotransmitter in the mammalian CNS, acts via ionotropic and metabotropic receptors. Results from in vitro studies demonstrating tight interactions between ionotropic NMDA receptors and subtype 5 metabotropic glutamate receptors (mGlu5) have shown that blockade of mGlu5 receptors increases the behavioral effects of NMDA receptor antagonists. The aim of the present work was to study the actions of the highly selective mGlu5 receptor antagonist MTEP alone and in combination with MK-801, a blocker of the NMDA receptor-associated ion channel, on performance of a delayed selection task (a test of working memory) in rats. MK-801 (0.1 mg/kg) induced a specific impairment to working memory, with proactive interference (degradation of the ability to remember current information because of the effects of previously learned material). Administration of MTEP (5.0 mg/kg) combined with both solvent and with MK-801 had no significant effects, demonstrating the small or nonexistent involvement of mGlu5 receptors in the mechanisms of working memory.

References

Dec 1, 1992·Archives of General Psychiatry·S Park, P S Holzman
Jan 1, 1990·European Archives of Psychiatry and Clinical Neuroscience·S Sahai
Jan 26, 1996·Neuroscience Letters·S M FitzjohnG L Collingridge
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Mar 11, 2004·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Houman HomayounBita Moghaddam
Sep 9, 2006·CNS Drug Reviews·Paul M Lea, Alan I Faden
Oct 3, 2007·Psychopharmacology·Irina A SukhotinaAnton Y Bespalov
Mar 8, 2008·Memory & Cognition·Tal Makovski, Yuhong V Jiang

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