title: NR2C by NR2B subunit exchange in juvenile mice affects emotionality and 5-HT in the frontal cortex.
abstract: The N-methyl-D-aspartate receptor (NMDA-R) has been inter alia implicated in synaptic plasticity, brain development and emotional processes. The NMDA-R is a multiprotein complex composed of NR1, NR2 and/or NR3 subunits. We generated NR2C-2B mutant mice in which an insertion of NR2B cDNA into the gene locus of the NR2C gene replaced NR2C by NR2B expression throughout the brain. This NR2C-2B mutant was used to examine whether an NMDA-R subunit exchange in juvenile mice would affect emotional behaviors and acetylcholine (ACh), dopamine (DA) and serotonin (5-HT) content in the frontal cortex (FC) and brain structures, which are part of the brain defense system, such as the periaqueductal grey matter (PAG). Juvenile, 1-month-old NR2C-2B mice showed increased open arm avoidance in the elevated plus-maze and increased fear-induced immobility. In terms of brain neurochemistry, NR2C-2B mice showed an increase in 5-HT levels in the FC at the age of 2 months. A correlational analysis revealed that mice with low open arms avoidance had high levels of ACh in the PAG but reduced 5-HT levels in the FC. Animals which showed high levels of fear-induced immobility also had high levels of 5-HT in the FC. These results suggest that the replacement of subunit NR2C by NR2B in juvenile mice increases anxiety- and fear-related behaviors possibly due to changes in FC-5-HT and PAG-ACh levels.
authors.affiliation: Institute of Physiological Psychology, Center for Biological and Medical Research, Heinrich-Heine-University of Düsseldorf, Düsseldorf, Germany.
authors.forename: M A
authors.initials: MA
authors.lastname: De Souza Silva
authors.forename: L
authors.initials: L
authors.lastname: Marchetti
authors.forename: U L M
authors.initials: UL
authors.lastname: Eisel
authors.forename: J P
authors.initials: JP
authors.lastname: Huston
authors.forename: E
authors.initials: E
authors.lastname: Dere
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004644:Emotions / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D005625:Frontal Lobe / Q000378:metabolism*; D046353:Immobility Response, Tonic / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010487:Periaqueductal Gray / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D011597:Psychomotor Performance / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D018709:Statistics, Nonparametric
chemical_list: C121001:NR2B NMDA receptor; C432823:NR2C NMDA receptor; D021122:Protein Subunits; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D012701:Serotonin; D000109:Acetylcholine; D004298:Dopamine