Tokishigyakukagoshuyushokyoto (TSGST) Inhibits Aggression Induced by Isolation Rearing in Mice

Herbal medicines are widely used in clinical practice. Several herbal medicines are prescribed in clinical practice to improve mental symptoms. Yokukansan is an effective prescription for irritability and aggression, which are behavioral and psychological symptoms of dementia (BPSD) or autism spectrum disorder (ASD). However, because herbal medicines contain many components, their pharmacological effects have not been analyzed in detail. Risperidone and quetiapine are prescribed in severe cases; however, their side effects of oversedation are problematic. Tokishigyakukagoshuyushokyoto (TSGST) is a herbal medicine prescribed to improve blood circulation and relieve headaches, back pain, or chilblains associated with hemodynamic insufficiency. Interestingly, most of the individual components of TSGST are known to exert sedative or analgesic effects. In this study, we investigated whether TSGST ameliorates aggressive behavior induced by social isolation in mice. The mice were isolated for 5 or 6 weeks immediately after weaning and given TSGST via a water bottle during this period. Long-term administration of TSGST suppressed the onset of aggression induced by isolation rearing. This aggressive phenotype was significantly reversed by intraperitoneal (i.p.) administration of the 5-hydroxytryptamine 1A (5-HT_1A) receptor antagonist WAY-100635 in TSGST-isolated mice. We also showed that TSGST had similar effects as risperidone, a commonly used antipsychotic for irritability and aggression. These results suggest that TSGST may be effective for irritability or aggression in BPSD or ASD.