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Diazepam improves aspects of social behaviour and neuron activation in NMDA receptor-deficient mice.

Genes, brain, and behavior (2014-07-22)
C A Mielnik, W Horsfall, A J Ramsey
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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
2,2,2-Tribromoethanol, 97%
Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, 99%
Sigma-Aldrich
2-Methyl-2-butanol, ReagentPlus®, ≥99%
Sigma-Aldrich
2-Methyl-2-butanol, anhydrous, ≥99%
Sigma-Aldrich
Diazepam
Sigma-Aldrich
Clozapine
Supelco
Diazepam solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
2-Methyl-2-butanol, analytical standard
Supelco
Diazepam solution, 1.0 mg/mL in methanol, analytical standard, for drug analysis
Clozapine, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Anti-c-Fos (Ab-2) (4-17) Rabbit pAb, liquid, Calbiochem®
USP
Clozapine, United States Pharmacopeia (USP) Reference Standard
Clozapine for peak identification, European Pharmacopoeia (EP) Reference Standard
Diazepam, European Pharmacopoeia (EP) Reference Standard
USP
Clozapine Resolution Mixture, United States Pharmacopeia (USP) Reference Standard