Systemic and prefrontal cortical NMDA receptor blockade differentially affect discrimination learning and set-shift ability in rats

Mark R. Stefani, Bita Moghaddam

Research output: Contribution to journalArticle

87 Scopus citations

Abstract

The authors examined discrimination rule learning and extradimensional set-shifting ability in rats given systemic or intracranial injections of the N-methyl-D-aspartate (NMDA) receptor antagonist MK801. Pretraining systemic injections of MK801 impaired both the acquisition of the initial discrimination rule (Set 1) and the shift to the 2nd rule (Set 2). Pretraining intramedial prefrontal cortical (mPFC) administration of MK801 did not impair Set 1 acquisition. Intra-mPFC injection of MK801 was previously found to impair Set 2 acquisition. Impaired Set 2 performance was due to increased cognitive perseveration. The data suggest that discrimination learning in naive subjects requires NMDA receptors outside the mPFC, whereas NMDA receptors within the mPFC are selectively involved in the modification of previous knowledge and/or the inhibition of previously learned responses.

Original languageEnglish (US)
Pages (from-to)420-428
Number of pages9
JournalBehavioral Neuroscience
Volume119
Issue number2
DOIs
StatePublished - Apr 1 2005

Keywords

  • Cognition
  • Glutamate
  • Prefrontal cortex
  • Schizophrenia
  • Wisconsin Card Sort Task

ASJC Scopus subject areas

  • Behavioral Neuroscience

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