Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice

João Costa-Nunes, Olga Zubareva, Margarida Araújo-Correia, Andreia Valença, Careen A Schroeter, Jodi L Pawluski, Julie Vignisse, Hellen Steinbusch, Denise Hermes, Marjan Phillipines, Harry M W Steinbusch, Tatyana Strekalova*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

33 Citations (Web of Science)


N-Methyl-D-aspartate receptor (NMDAR)-mediated neurotransmission in the hippocampus is implicated in cognitive and emotional disturbances during stress-related disorders. Here, using quantitative RT-PCR, we investigated the hippocampal expression of NR2A, NR2B and NR1 subunit mRNAs in a mouse stress paradigm that mimics clinically relevant conditions of simultaneously affected emotionality and hippocampus-dependent functions. A 2-week stress procedure, which comprised ethologically valid stressors, exposure to a rat and social defeat, was applied to male C57BL/6J mice. For predation stress, mice were introduced into transparent containers that were placed in a rat home cage during the night; social defeat was applied during the daytime using aggressive CD1 mice. This treatment impaired hippocampus-dependent performance during contextual fear conditioning. A correlation between this behavior and food displacement performance was demonstrated, suggesting that burrowing behavior is affected by the stress procedure and is hippocampus-dependent. Stressed mice (n = 22) showed behavioral invigoration and anomalous anxiolytic-like profiles in the O-maze and brightly illuminated open field, unaltered short-term memory in the step-down avoidance task and enhanced aggressive traits, as compared to non-stressed mice (n = 10). Stressed mice showed increased basal serum corticosterone concentrations, hippocampal mRNA expression for the NR2A subunit of the NMDAR and in the NR2A/NR2B ratio; mRNA expression of NR2B and NR1 was unchanged. Thus, stress-induced aberrations in both hippocampal-dependent performance and emotional abnormalities are associated with alterations in hippocampal mRNA NR2A levels and the NR2A/NR2B ratio and not with mRNA expression of NR2B or NR1.

Original languageEnglish
Pages (from-to)108-16
Number of pages9
JournalStress-the International Journal on the Biology of Stress
Issue number1
Publication statusPublished - Jan 2014


  • Aggression
  • Animals
  • Behavior, Animal
  • Corticosterone
  • Emotions
  • Fear
  • Hippocampus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Tissue Proteins
  • RNA, Messenger
  • Rats
  • Receptors, N-Methyl-D-Aspartate
  • Social Dominance
  • Stress, Psychological

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