The investigation of neonatal MK-801 administration and physical environmental enrichment on emotional and cognitive functions in adult Balb/c mice

Pharmacol Biochem Behav. 2012 Sep;102(3):407-14. doi: 10.1016/j.pbb.2012.06.006. Epub 2012 Jun 12.


N-methyl-D-aspartate (NMDA) receptors play an important role in brain maturation and developmental processes. It is known that growing up in an enriched environment has effects on emotional and cognitive performance. In our study, we evaluated the effects of physically enriched environment on the emotional and cognitive functions of the adult brain in the setting of previous NMDA receptor hypoactivity during the critical developmental period of the nervous system. In this study, NMDA receptor blockade was induced 5-10 days postnatally (PD5-10) using MK-801 in mice Balb/c (twice a day 0.25 mg/kg, for 5 days, intraperitoneal). MK-801 was given to developing mice living in a standard (SE) and an enrichment environment (EE) and once the animals reached adulthood, emotional behaviors were evaluated using an open field test (OF) and an elevated plus maze (EPM) test whereas cognitive processes were evaluated using the Morris water-maze (MWM). The EE group showed decreased locomotor activity (p<0.05) in the OF and increased exploratory behaviour (p<0.01) and decreased fear of heights/anxiety-like behaviour (p<0.05) in the EPM test. The EE had positive effects on spatial learning in the MWM (p<0.05). Blockade of the NMDA receptor increased the fear of height (p<0.05), decreased exploratory behaviour and locomotor activity (p<0.001). Also, it led to decreased spatial learning (p<0.05). The decreases in spatial learning and exploratory behaviours and the increase in fear of heights/anxiety-like behaviour with NMDA receptor blockade was not reversed by EE. NMDA receptor blockade during the critical period of development led to deterioration in the emotional and cognitive processes during adulthood. An enriched environmental did not reverse the deleterious effects of the NMDA receptor blockade on emotional and cognitive functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Anxiety / psychology
  • Body Weight / drug effects
  • Body Weight / physiology
  • Brain / growth & development
  • Cognition / drug effects*
  • Critical Period, Psychological
  • Dizocilpine Maleate / pharmacology*
  • Emotions / drug effects*
  • Environment*
  • Exploratory Behavior / drug effects
  • Growth / drug effects
  • Learning / drug effects
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Swimming / physiology


  • Neuroprotective Agents
  • Dizocilpine Maleate