Effects of NMDA and Metabotropic Glutamate Receptors Antagonists in Working Memory Task in Rats

Glutamate, major excitatory neurotransmitter in mammalian CNS, acts via ionotropic and metabotropic receptors. In agreement with the results of in vitro studies that pointed at close interactions between ionotropic NMDA and metabotropic glutamate mGlu5 receptors, blockade of mGlu5 receptors was reported to enhance behavioral effects of NMDA receptor channel blockers. The present study aimed to study the effects of a highly selective mGluR5 antagonist MTEP, alone and in combination with NMDA receptor channel blocker MK-801, in rats trained to perform a delay-non-match-to-position task (working memory test). Acute administration of MK-801 (0.1 mg/kg) produced specific working memory impairment expressed as proactive interference (poor performance in the current trial due to the interfering influence of the experience in past trials). However, administration of MTEP (5.0 mg/kg), either alone or in combination with MK-801, had no appreciable effects. While these data clearly indicate little or no involvement of mGlu5 receptors in the mechanisms of working memory, present results demonstrate a robust experimental approach to study cognitive deficits associated with psychotomimetic drug treatment.