Saiko-ka-ryukotsu-borei-to, an herbal medicine, prevents chronic stress-induced disruption of glucocorticoid negative feedback in rats

Exposure to stress is known to precipitate or exacerbate many neuropsychiatric disorders such as depression. Abnormality of the neuroendocrine system, as shown by increased adrenal weight and attenuated glucocorticoid negative feedback, is frequently seen in depression. The aim of the present study is to clarify the usefulness of saiko-ka-ryukotsu-borei-to, an herbal medicine, in the treatment of abnormality of the neuroendocrine system using an experimental stress-depression model. Rats were subjected to water immersion and restraint for 2 h daily for 4 weeks (chronic stress), followed by recovery for 10 days. Saiko-ka-ryukotsu-borei-to was administered during the stress and recovery periods (100, 300, or 1000 mg/kg daily, p.o.) or only during the recovery period (1000 mg/kg). After the recovery period, the adrenal weight was measured, and glucocorticoid feedback ability was evaluated by a dexamethasone suppression test using 30 mug/kg dexamethasone. The administration of saikoka-ryukotsu-borei-to during the stress and recovery periods prevented the stress-induced increase in adrenal weight or the attenuated negative feedback in a dose-dependent manner. The administration of saiko-ka-ryukotsu-borei-to during the recovery period alone also ameliorated the abnormality of the neuroendocrine system. these results indicate that saiko-ka-ryukotsu-borei-to is effective against chronic stress-induced abnormality of the neuroendocrine system. Because some symptoms and symptomatic relapses in depressives are attributed to dysfunction of the hypothalamo-pituitary-adrenal axis, the present findings provide information important for prevention and treatment of depression. (C) 2002 Elsevier Science Inc. All rights reserved.