Abstract
[Background and Purpose] A mouse aggressive response meter (ARM) is a device that measures aggressive biting behavior (ABB) toward a metal rod presented in front of a mouse. With this device, we have previously found that kamishoyosan, a Japanese traditional herbal medicine, reduces this aggressive behavior (Igarashi et al., Brain Res. 2021). Although, in the previous study, it was suggested that males and females have different effects on GABAA receptors, the details have not been clarified. In this study, we investigated the effects of diazepam, an agonist for GABAA receptors.
[Experimental methods and results] Male and female ddY mice were isolation-reared from 3 to 10 to 11 weeks after birth. Isolation-reared male mice showed a 51% decrease in ABB 1 hour after i.p. administration with 2 mg/kg diazepam (p<0.05). On the other hand, no significant changes were observed in female mice treated with 2mg/kg diazepam. ABB was reduced by approximately 63% in male and 53% in female mice treated with 4 mg/kg diazepam (p<0.05). Next, we examined the expression level of potassium-chloride ion transporter (KCC2) mRNA in the prefrontal cortex by real-time PCR, and we found that it was decreased to about 8% in isolation-reared female mice compared to group-reared female mice (p<0.05). No significant difference was found between isolated and group-housed male mice.
[Discussion] KCC2 contributes inhibitory neural transmission by exporting intracellular chloride ion (Cl-). In this study, KCC2 expression in the PFC was decreased only in isolated female mice, which may disturb inhibitory neural transmission, consequently make it difficult for diazepam to reduce aggression.
