The 5-HT2A receptor antagonist M100,907 prevents extracellular glutamate rising in response to NMDA receptor blockade in the mPFC

Ilaria Ceglia, Mirjana Carli, Marta Baviera, Giuliano Renoldi, Eleonora Calcagno, Roberto W. Invernizzi

Research output: Contribution to journalArticle

Abstract

We recently found that intracortical injection of the selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist 3-(R)-2- carboxypiperazin-4-propyl-1-phosphonic acid (CPP) impaired attentional performance in rats and blockade of 5-hydroxytryptamine (5-HT)2A receptors antagonized this effect. Here, we used the microdialysis technique in conscious rats to study the effect of CPP on extracellular glutamate (GLU) in the medial prefrontal cortex (mPFC) and the regulation of this effect by 5-HT2A receptors. Intraperitoneal injection of 20 mg/kg CPP increased extracellular GLU in the mPFC (201% of basal levels) but had no effect on 5-HT. Intracortical infusion of 100 μM CPP increased extracellular GLU (230% of basal values) and 5-HT (150% of basal values) in the mPFC, whereas 30 μM had no significant effect. The effect of 100 μM CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 μg/kg M100,907 completely antagonized the effect of 100 μM CPP on extracellular GLU, whereas 10 μg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 μM M100,907 completely reversed the increase of extracellular GLU induced by CPP. These findings show that blockade of NMDA receptors in the mPFC is sufficient to increase extracellular GLU locally. The increase of cortical extracellular GLU may contribute to CPP-induced cognitive deficits and blockade of 5-HT2A receptors may provide a molecular mechanism for reversing these deficits caused by dysfunctional glutamatergic transmission in the mPFC.

Original languageEnglish
Pages (from-to)189-199
Number of pages11
JournalJournal of Neurochemistry
Volume91
Issue number1
DOIs
Publication statusPublished - Oct 2004

Keywords

  • 5-HT2A receptors
  • 907
  • CPP
  • Glutamate
  • M100
  • Medial prefrontal cortex
  • NMDA receptors

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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