title: Diazepam improves aspects of social behaviour and neuron activation in NMDA receptor-deficient mice.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
authors.forename: C A
authors.initials: CA
authors.lastname: Mielnik
authors.forename: W
authors.initials: W
authors.lastname: Horsfall
authors.forename: A J
authors.initials: AJ
authors.lastname: Ramsey
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003024:Clozapine / Q000494:pharmacology; D003975:Diazepam / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D009928:Organ Specificity; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D012919:Social Behavior
chemical_list: C121673:Gprin1 protein, mouse; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D003024:Clozapine; D003975:Diazepam
keywords: Antipsychotic; GABA; NMDA; benzodiazepine; glutamate; neural substrate; social behaviour