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

摘要: 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 blockade 5-hydroxytryptamine (5-HT)2A receptors antagonized this effect. Here, we used microdialysis technique conscious to study effect CPP on extracellular glutamate (GLU) medial prefrontal cortex (mPFC) regulation by 5-HT2A receptors. Intraperitoneal 20 mg/kg increased GLU mPFC (201% basal levels) but had no 5-HT. Intracortical infusion 100 lM (230% values) 5-HT (150% mPFC, whereas 30 significant The was abolished tetrodotoxin, suggesting neuronal activity is required. Subcutaneous 40 lg/kg M100,907 completely GLU, 10 caused only partial attenuation. Likewise, 0.1 reversed increase induced CPP. These findings show NMDA sufficient locally. cortical may contribute CPP-induced cognitive deficits provide a molecular mechanism for reversing these dysfunctional glutamatergic transmission