title: Altered emotionality, hippocampus-dependent performance and expression of NMDA receptor subunit mRNAs in chronically stressed mice.
abstract: 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.
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University , Maastricht , the Netherlands .
authors.forename: João
authors.initials: J
authors.lastname: Costa-Nunes
authors.forename: Olga
authors.initials: O
authors.lastname: Zubareva
authors.forename: Margarida
authors.initials: M
authors.lastname: Araújo-Correia
authors.forename: Andreia
authors.initials: A
authors.lastname: Valença
authors.forename: Careen A
authors.initials: CA
authors.lastname: Schroeter
authors.forename: Jodi L
authors.initials: JL
authors.lastname: Pawluski
authors.forename: Julie
authors.initials: J
authors.lastname: Vignisse
authors.forename: Hellen
authors.initials: H
authors.lastname: Steinbusch
authors.forename: Denise
authors.initials: D
authors.lastname: Hermes
authors.forename: Marjan
authors.initials: M
authors.lastname: Phillipines
authors.forename: Harry M W
authors.initials: HM
authors.lastname: Steinbusch
authors.forename: Tatyana
authors.initials: T
authors.lastname: Strekalova
mesh_terms: D000374:Aggression / Q000523:psychology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D004644:Emotions; D005239:Fear / Q000523:psychology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis*; D012930:Social Dominance; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: C121673:Gprin1 protein, mouse; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D003345:Corticosterone