Open AccessDiazepam improves aspects of social behaviour and neuron activation in NMDA receptor‐deficient mice
Author(s) -
Mielnik C. A.,
Horsfall W.,
Ramsey A. J.
Publication year - 2014
Publication title -
genes, brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.315
H-Index - 91
eISSN - 1601-183X
pISSN - 1601-1848
DOI - 10.1111/gbb.12155
Subject(s) - clozapine , nmda receptor , neuroscience , stimulation , amygdala , psychology , cingulate cortex , septal nuclei , diazepam , ventral tegmental area , thalamus , social identity approach , hippocampus , c fos , cortex (anatomy) , receptor , medicine , chemistry , central nervous system , schizophrenia (object oriented programming) , psychiatry , dopamine , gene expression , social psychology , dopaminergic , social identity theory , social group , biochemistry , gene
NR1 knockdown (NR1KD) mice are genetically modified to express low levels of the NR1 subunit of N ‐methyl‐ d ‐aspartate (NMDA) receptors, and show deficits in affiliative social behaviour. In this study, we determined which brain regions were selectively activated in response to social stimulation and asked whether differences in neuronal activation could be observed in mice with reduced sociability. Furthermore, we aimed to determine whether brain activation patterns correlated with the amelioration of social deficits through pharmacological intervention. The cingulate cortex, lateral septal nuclei, hypothalamus, thalamus and amygdala showed an increase in c‐Fos immunoreactivity that was selective for exposure to social stimuli. NR1KD mice displayed a reduction in social behaviour and a reduction in c‐Fos immunoreactivity in the cingulate cortex and septal nuclei. Acute clozapine did not significantly alter sociability; however, diazepam treatment did increase sociability and neuronal activation in the lateral septal region. This study has identified the lateral septal region as a neural substrate of social behaviour and the GABA system as a potential therapeutic target for social dysfunction.