Postnatal MK-801 treatment of female rats impairs acquisition of working memory, but not reference memory in an eight-arm radial maze; no beneficial effects of enriched environment

Psychopharmacology (Berl). 2015 Jul;232(14):2541-50. doi: 10.1007/s00213-015-3890-5. Epub 2015 Mar 7.


Rationale: Memory impairment has been documented in MK-801 (NMDA receptor antagonist) model of schizophrenia, but less is known on the rescue and/or differential effects of MK-801 on short- and long-term memories.

Objectives: We determined the effects of MK-801 treatment and/or enriched environment (EE) on acquisition of reference and working memory in developing rats.

Methods: Female Wistar rats were injected with MK-801 (1 mg/kg) from postnatal days (P) 6-10. Task acquisition, working memory error (WME), and reference memory error (RME) were assessed in an eight-arm radial maze task. Behavioral performance of rats was also tested in an open field test before (P35-P40) and after (P65-P70) radial maze training to assess anxiety and locomotion. EE was applied from birth up to the end of experiments.

Results: MK-801 treatment did not influence task acquisition in the radial maze; however, by the end of training, MK-801-treated rats made significantly more WME, but not RME, compared to control rats. Ratio of WME to total error was also significantly higher in MK-801 group. EE prevented MK-801-associated behaviors in the open field but did not exert beneficial effects on working memory deficit in the radial maze task. EE per se affected behavioral performance of rats only in the open field test.

Conclusions: Our results suggest that postnatal MK-801 treatment differentially affects working and reference memory in a young brain. Anxiety and hyperactivity associated with MK-801 are observed more severely in adulthood. Dissociation of the positive effects of EE may suggest selective modification of distinct pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / psychology
  • Dizocilpine Maleate / pharmacology*
  • Environment*
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Female
  • Maze Learning / drug effects*
  • Memory, Long-Term / drug effects*
  • Memory, Short-Term / drug effects*
  • Motor Activity / drug effects
  • Pregnancy
  • Rats
  • Rats, Wistar


  • Excitatory Amino Acid Antagonists
  • Dizocilpine Maleate