Abstract
Kososan (Xiang-Su-San in Chinese), a Kampo (Japanese herbal) medicine, has been used clinically in East Asia for the treatment of depressive symptom associated with the common cold, allergy, insomnia and autonomic imbalance. The therapeutic use of interferon (IFN)-α is known to cause various neuropsychiatric adverse effects, and especially, there is a problem in which IFN-α therapy in patients with hepatitis C often induces the depressive symptom. However, the antidepressive effect of kososan on the IFN-α-induced depression remains unclear. In the present study, we investigated whether kososan improves depressive-like behaviors in IFN-α-induced depressive-like model mice. The degree of the depressive-like state was measured by the animal's duration of immobility using a forced swimming test (FST). Oral administration of kososan (1.0 g/kg/day, 14 days) significantly reduced the duration of immobility time of IFN-α (1.2 x 106 IU/kg/day, 7 days, i.p.)-induced depressive-like model in the FST; however, locomotor activity was not affected. Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis plays a crucial role in the pathology of depression. IFN-α-induced increases in corticotropin-releasing hormone mRNA expression in the hypothalamus and corticosterone levels of sera were decreased by the administration of kososan. These results suggest that kososan shows an antidepressive-like effect via normalizing the hyperactivity of HPA axis in the IFN-α-induced depressive-like model mice.
