title: Saiko-ka-ryukotsu-borei-to, a herbal medicine, ameliorates chronic stress-induced depressive state in rotarod performance.
abstract: Exposure to chronic stress is thought to play an important role in the etiology of depression. This disorder has been shown to involve disruption of the hypothalamo-pituitary-adrenal (HPA) system and dysfunction of the prefrontal cortex (PFC). We have demonstrated that chronic stress in rats induces similar HPA disruption or a depressive state caused by a reduction of dopaminergic and serotonergic transmission in the PFC. We have also shown that saiko-ka-ryukotsu-borei-to, a herbal medicine, prevents such chronic stress-induced HPA disruption. However, the behavioral and neurochemical bases of this drug remain unclear. Here we examined the effects of saiko-ka-ryukotsu-borei-to on the depressive behavioral state and the reduction of transmission resulting from chronic stress. The chronic stress was induced by water immersion and restraint (2 h/day) for 4 weeks followed by recovery for 10 days. The treatment with saiko-ka-ryukotsu-borei-to (100, 300, or 1000 mg/kg p.o.) ameliorated the stress-induced depressive state in a dose-dependent manner, evaluated by a rotarod test. A microdialysis study indicated that the drug treatment significantly prevented the chronic stress-induced decreases in extracellular concentrations of dopamine and serotonin in the PFC. These results suggest that saiko-ka-ryukotsu-borei-to ameliorates the chronic stress-induced depressive state based on the prevention of PFC dysfunction. These findings provide important information for treatment of depression.
authors.affiliation: Pharmacology Department, Central Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-1192, Japan. mizoguchi_kazushige@mail.tsumura.co.jp
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Yuzurihara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishige
authors.forename: Masaki
authors.initials: M
authors.lastname: Aburada
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tabira
mesh_terms: D000818:Animals; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology*; D004298:Dopamine / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005110:Extracellular Space / Q000378:metabolism; D018737:Hand Strength / Q000502:physiology; D008297:Male; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications* / Q000523:psychology*
chemical_list: D004365:Drugs, Chinese Herbal; C095444:saiko-ka-ryukotsu-borei-to; D012701:Serotonin; D004298:Dopamine