NMDA receptor antagonists impair prefrontal cortex function as assessed via spatial delayed alternation performance in rats: Modulation by dopamine

Anita Verma, Bita Moghaddam

Research output: Contribution to journalArticle

373 Citations (Scopus)

Abstract

The present study was performed to assess the role of excitatory amino acid and dopamine receptors on associative functions of the prefrontal cortex (PFC) of the rat. Spatial delayed alternation was used as a PFC-sensitive cognitive task. In addition, in vivo microdialysis was used to assess the release of dopamine in the PFC. The noncompetitive NMDA antagonists ketamine (10-30 mg/kg) and MK-801 (0.1 and 0.5 mg/kg) dose-dependently impaired the spatial delayed alternation performance compared with the saline-treated control group. Administration of the dopamine antagonists raclopride (0.1 and 0.5 mg/kg), SCH-23390 (0.1 mg/kg), or haloperidol (0.1 mg/kg) was without a significant effect. However, haloperidol and raclopride (but not SCH-23390) reversed the disruptive effect of 30 mg/kg ketamine on spatial delayed alternation performance. Microdialysis studies revealed that this dose of ketamine preferentially increased the release of dopamine in the PFC compared with the striatum. These findings indicate that attenuation of glutamatergic neurotransmission at the NMDA receptor impairs PFC-dependent cognitive functions. Furthermore, activation of dopamine neurotransmission contributes, at least in part, to this impairment.

Original languageEnglish (US)
Pages (from-to)373-379
Number of pages7
JournalJournal of Neuroscience
Volume16
Issue number1
StatePublished - Jan 1 1996
Externally publishedYes

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Prefrontal Cortex
N-Methyl-D-Aspartate Receptors
Dopamine
Ketamine
Raclopride
Microdialysis
Haloperidol
Synaptic Transmission
Dizocilpine Maleate
Dopamine Antagonists
Dopamine Receptors
Glutamate Receptors
N-Methylaspartate
Cognition
Control Groups
SCH 23390

Keywords

  • antipsychotic drugs
  • delayed alternation
  • dopamine
  • glutamate
  • microdialysis
  • NMDA receptors
  • prefrontal cortex
  • schizophrenia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

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