Kamikihito ameliorates social recognition in oxytocin gene deficient mice and environmentally induced autism spectrum disorder model mice

Abstract

Ethnopharmacological relevance: Kamikihito (KKT) is a traditional Japanese medicine used to treat insomnia, anemia, anxiety and neurosis. Its scientific mechanism of action is not well understood.

Aim of the study: This study aimed to evaluate the therapeutic effect of KKT on deficits in social recognition ability, a phenotype of autism spectrum disorder (ASD), and to investigate the involvement of oxytocin in its action.

Materials and methods: KKT was orally administered to wild-type (WT), Oxytocin knockout (Oxt (-/-)), and Oxt receptor knockout (Oxtr (-/-)) mice, and social recognition ability was assessed using a three-chamber test. Neuronal activation changes in the brain after social stimulation were evaluated using c-Fos immunostaining in WT, Oxt (-/-), and Oxt (-/-) mice treated with KKT. Additionally, we examined whether KKT ameliorates social recognition impairment in LPS-induced ASD model mice (LPS mice), where LPS serves as an environmental factor.

Results: Abnormal social recognition behavior was improved in the Oxt (-/-) mice after sustained KKT administration, but not in the Oxtr (-/-) mice. c-Fos immunostaining revealed excessive neural activation of the Oxt (-/-) mice following social stimulation, which was reduced to WT levels after KKT administration. Social recognition impairment in the LPS mice was improved by KKT.

Conclusion: Our results suggest that KKT may improve social recognition by acting through Oxtr and by suppressing excessive neural activation after social stimulation. These effects may represent part of KKT's mechanism of action. It is possible for KKT to become a commonly used treatment for ASD-like symptoms.

Keywords: Autism spectrum disorder; Kamikihito; Lipopolysaccharide-induced inflammation; Oxytocin; Oxytocin receptor; Social recognition.