The serotonin 5-HT2A receptors antagonist MI00907 prevents impairment in attentional performance by NHDA receptor blockade in the rat prefrontal cortex

Carli Mirjana, Marta Baviera, Roberto W. Invernizzi, Claudia Balducci

Research output: Contribution to journalArticle

Abstract

We investigated whether 5-HT2A receptors contribute to the control of attentional performance by glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC). We examined the effects of NMDA receptor blockade in the mPFC on attentional performance by infusing a competitive glutamate NMDA receptor antagonist, 3-(R)-2-carboxypiperazin-4-propyl-1- phosphonic acid (CPP) into the mPFC of rats performing a task of divided and sustained visual attention. The five-choice serial reaction time task provides indices of attentional functioning (% correct responses), executive control (measured by anticipatory and perseverative responses) and speed. A dose of 10 ng CPP injected bilaterally into the mPFC increased anticipatory and perseverative responding; 50 ng reduced accuracy. Increasing the stimulus duration alleviated the CPP-induced accuracy deficit but did not reduce its effects on anticipatory and perseverative responses. CPP at 50 ng caused motor hyperactivity whereas lower doses had no effect. [R-(+)-(2,3-dimethoxyphenyl)-1- [2-(4-fluorophenyiethyl)]-4-piperidine-methanol] (MI00907) (MI00907), a 5-HT2A receptor antagonist, injected subcutaneously at 10 and 40 μg/kg, had no effect on accuracy but dose dependently reversed the impairment induced by 50 ng CPP. Both doses of M100907 completely abolished CPP-induced anticipatory but not perseverative over-responding. At the dose of 40 μg/kg M100907 reversed CPP-induced motor hyperactivity. This study provides evidence that the prefronto-cortical glutamate NMDA system may make an important contribution to the control of attention and executive functions. It also indicates that 5-HT2A receptors may serve to optimize attentional selectivity and improve some aspects of executive control.

Original languageEnglish
Pages (from-to)1637-1647
Number of pages11
JournalNeuropsychopharmacology
Volume29
Issue number9
DOIs
Publication statusPublished - Sep 2004

Keywords

  • 3-(R)-2-carboxypiperazin-4- propyl-1-phosphonic acid (CPP)
  • 5-CSRT task
  • 5-HT receptors
  • Attention
  • Executive functions
  • Glutamate NMDA receptors
  • Medial prefrontal cortex

ASJC Scopus subject areas

  • Pharmacology

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