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

Journal of Neurochemistry
Ilaria CegliaRoberto W Invernizzi

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 microm CPP increased extracellular GLU (230% of basal values) and 5-HT (150% of basal values) in the mPFC, whereas 30 microm had no significant effect. The effect of 100 microm CPP on extracellular GLU was abolished by tetrodotoxin, suggesting that neuronal activity is required. Subcutaneous injection of 40 microg/kg M100,907 completely antagonized the effect of 100 microm cpp on extracellular GLU, whereas 10 microg/kg caused only partial attenuation. Likewise, intracortical infusion of 0.1 microm M100,907 completely reversed the increase of extracellular GL...Continue Reading

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Citations

Sep 4, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Benoit LabonteGabriella Gobbi
Jul 8, 2005·Psychopharmacology·Charles H LargeDonald C Goff
Jan 21, 2012·Molecular Neurobiology·Katsuhiko MiyazakiKenji Doya
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Sep 6, 2007·Proceedings of the National Academy of Sciences of the United States of America·Lucila KargiemanFrancesc Artigas
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Jul 12, 2017·Progress in Neuro-psychopharmacology & Biological Psychiatry·Milena GirottiDavid A Morilak
Dec 27, 2008·Pharmacology & Therapeutics·V J AloyoJ A Harvey

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