N-methyl-D-aspartate receptor antagonist MK-801 and spatial memory representation: working memory is impaired in an unfamiliar environment but not in a familiar environment

Behav Neurosci. 1992 Aug;106(4):604-12. doi: 10.1037//0735-7044.106.4.604.


Female Sprague-Dawley rats were injected with the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 or saline 30 min before daily testing in spatial working memory (WM) and reference memory (RM) procedures in an 8-arm radial maze. MK-801 impaired RM and WM acquisition but not performance when rats were trained to criterion before drug administration. Neither a 2-hr nor a 4-hr delay between the first and last 2 correct WM choices impaired long-term WM. MK-801 impaired WM performance in trained rats only when rats were tested in a new environment. Thus, 2 mechanisms may be required for relational memory: an NMDA-dependent mechanism for acquiring long-term spatial representations and an NMDA-insensitive mechanism for operating on these stored representations.

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects
  • Discrimination Learning / drug effects*
  • Dizocilpine Maleate / pharmacology*
  • Dose-Response Relationship, Drug
  • Female
  • Hippocampus / drug effects*
  • Mental Recall / drug effects*
  • Orientation / drug effects*
  • Rats
  • Rats, Inbred Strains
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Retention, Psychology / drug effects*
  • Social Environment*


  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate