Aim Ninjinyoeito (NYT) and kamikihito (KKT) are two types of a group of Japanese herbal medicines called ‘Kampo‐hozai’, which can improve depleted mental and physical energy in a variety of patients. NYT and KKT are therefore also expected to improve the symptoms of aging. However, evidence of the therapeutic effects of NYT and KKT on age‐related mental disorders in basic research remains scarce. The present study examined the effects of NYT and KKT on mental disorder‐like behaviors in senescence‐accelerated mouse‐prone 8 (SAMP8) mice, a model of accelerated aging. Methods SAMP8 mice were orally administered NYT or KKT (300 or 1000 mg/kg/d) starting from 12 weeks of age. A splash test was conducted at 21 weeks of age. An open‐field test was conducted at 20 and 33–34 weeks of age. Results Treatment with NYT, but not KKT, increased the grooming time of SAMP8 mice in the splash test at 21 weeks of age, suggesting that NYT ameliorates apathy‐like behavior. In contrast, treatment with KKT, but not NYT, increased the time spent by SAMP8 mice in the inner zone of the open‐field test at 33–34 weeks of age, suggesting that KKT ameliorates anxiety‐like behavior. Conclusion NYT and KKT may be useful for treating apathy and anxiety, respectively, in older individuals.

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Aim: Ninjinyoeito (NYT) is a Kampo medicine prescribed for patients with decreased mental and physical energy. Clinical studies demonstrate that NYT ameliorates depressive symptoms in patients with various diseases. However, the underlying therapeutic mechanisms of action remain unclear. The monoaminergic system has been implicated in the neuropathology of depression. Using immobility in the tail suspension test to evaluate depression-like behavior, we aimed to examine the effects of NYT and the involvement of the α 1 -adrenoceptor and serotonin (5-HT) 1A receptor in its mechanism of action. Methods: Immobility in the tail suspension test was used as an index of depression-like behavior. NYT (1,000 or 2,000 mg/kg/ day, once a day for seven days) was orally administered to mice. Prazosin and WAY-100635 were administered 30 min and 1 h before the test, respectively. Norepinephrine (NE) and 5-HT levels in the frontal cortex and amygdala were analyzed using a high-performance liquid chromatography (HPLC) electrochemical detector. Results: NYT (2000 mg/kg/day) shortened the immobility time. Prazosin and WAY-100635 blocked the NYT-mediated reduction in immobility time. NYT increased NE levels, but not 5-HT levels, in the amygdala. Conclusion: NYT reduced immobility time in the tail suspension test, likely by increasing NE levels. The increased NE levels may activate the α 1 -adrenoceptor, thereby ameliorating the depression-like behavior. NYT may therefore improve depressive symptoms in patients by enhancing the noradrenergic system.