The 5-HT1A receptor agonist 8-OH-DPAT prevents prefrontocortical glutamate and serotonin release in response to blockade of cortical NMDA receptors

E. Calcagno, M. Carli, R. W. Invernizzi

Research output: Contribution to journalArticle

Abstract

We studied the role of 5-HT1A receptors in controlling the release of glutamate (GLU) in the medial prefrontal cortex (mPFC) of conscious rats with the in vivo microdialysis technique. The effect of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin infused in the prefrontal cortex was examined under basal conditions and on the rise of extracellular GLU (+106%) induced by co-infusion of the competitive N-methyl-d-aspartate receptor antagonist 3-[(R)-2-carboxypiperazin-4yl]-propyl- 1-phosphonic acid (CPP). 8-OH-DPAT (0.3 and 3 μm) had no effect on basal extracellular GLU, but the higher concentration completely abolished the rise of extracellular GLU induced by CPP. CPP also increased extracellular serotonin (5-HT) in the mPFC (+50%) and this effect was antagonized by 3 μm 8-OH-DPAT which, by itself, had no effect on basal 5-HT release. The effects of 8-OH-DPAT on extracellular GLU and 5-HT were reversed by the 5-HT1A receptor antagonist WAY100 635 (100 μm), indicating a selective involvement of 5-HT1A receptors. WAY100 635 had no effect by itself. These results show that the stimulation of cortical 5-HT1A receptors prevents the CPP-evoked rise of extracellular GLU and 5-HT and suggest that these effects may contribute to the ability of intracortical 8-OH-DPAT to counteract cognitive deficitsq2 caused by the blockade of NMDA receptors.

Original languageEnglish
Pages (from-to)853-860
Number of pages8
JournalJournal of Neurochemistry
Volume96
Issue number3
DOIs
Publication statusPublished - Feb 2006

Keywords

  • 5-HT receptors
  • Glutamate release
  • Medial prefrontal cortex
  • NMDA receptor antagonists
  • Serotonin release
  • WAY100 635

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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