Enriched environment has limited capacity for the correction of hippocampal memory-dependent schizoid behaviors in rats with early postnatal NMDAR dysfunction

Int J Dev Neurosci. 2014 Apr;33:22-8. doi: 10.1016/j.ijdevneu.2013.10.004. Epub 2013 Oct 30.


Pre- and early postnatal stress can cause dysfunction of the N-methyl-d-aspartate receptor (NMDAR) and thereby promote the development of hippocampus memory-dependent schizoid abnormalities of navigation in space, time, and knowledge. An enriched environment improves mental abilities in humans and animals. Whether an enriched environment can prevent the development of schizoid symptoms induced by neonatal NMDAR dysfunction was the central question of our paper. The experimental animals were Wistar rats. Early postnatal NMDAR dysfunction was created by systemic treatment of rat pups with the NMDAR antagonist MK-801 at PD10-20 days. During the development period (PD21-90 days), the rats were reared in cognitively and physically enriched cages. Adult age rats were tested on navigation based on pattern separation and episodic memory in the open field and on auto-hetero-associations based on episodic and semantic memory in a step-through passive avoidance task. The results showed that postnatal NMDAR antagonism caused abnormal behaviors in both tests. An enriched environment prevented deficits in the development of navigation in space based on pattern separation and hetero-associations based on semantic memory. However, an enriched environment was unable to rescue navigation in space and auto-associations based on episodic memory. These data may contribute to the understanding that an enriched environment has a limited capacity for therapeutic interventions in protecting the development of schizoid syndromes in children and adolescents.

Keywords: Auto-hetero-associations; Environmental enrichment; Hippocampus; Navigation; Neonatal NMDAR antagonism; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Animals, Newborn
  • Avoidance Learning / drug effects
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology
  • Environment*
  • Excitatory Amino Acid Antagonists / pharmacology
  • Fear / psychology
  • Female
  • Hippocampus / physiopathology*
  • Male
  • Memory Disorders / etiology*
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Receptors, N-Methyl-D-Aspartate / metabolism*
  • Schizoid Personality Disorder* / complications
  • Schizoid Personality Disorder* / nursing
  • Schizoid Personality Disorder* / pathology


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