The NMDA-receptor antagonist MK-801 selectively disrupts reversal learning in rats

Neuroreport. 2003 Dec 2;14(17):2225-8. doi: 10.1097/00001756-200312020-00018.


We tested the hypothesis that inhibition of NMDA-receptors in rats would lead to a selective impairment of reversal learning in a serial reversal task in the Skinner box. Low doses of MK-801 (0.025 and 0.05 mg/kg) did not affect acquisition of the two-lever discrimination, but impaired performance during the first reversal more than during the third reversal. Similar effects were observed during the series of extinction sessions. The high dose (0.1 mg/kg) completely inhibited reversal and extinction learning, as the rats perseverated in pressing the previously rewarded lever(s). We conclude that NMDA receptor blockade leads to a selective impairment in cognitive flexibility, and shows some similarity to transient inactivation of the medial prefrontal cortex in this respect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dizocilpine Maleate / pharmacology*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Reversal Learning / drug effects*
  • Reversal Learning / physiology


  • Excitatory Amino Acid Antagonists
  • Receptors, N-Methyl-D-Aspartate
  • Dizocilpine Maleate