title: Antistress effects of Kampo medicine "Yokukansan" via regulation of orexin secretion.
abstract: OBJECTIVE
  Various stressors induce stress responses through the hypothalamic-pituitary-adrenal and the sympathetic-adrenal-medullary axes, which are regulated, in part, by orexin. For example, secretion of orexin in the hypothalamus is increased in rats exposed to the stress of social isolation for 1 week. In this study, the antistress effects of Kampo medicine Yokukansan (YKS) via the regulation of orexin secretion were investigated using a rat model.
  
  
  RESULTS
  The administration of 300 mg/kg per day of YKS to rats for 1 week significantly decreased the plasma orexin levels compared with non-treated rats, whereas the administration of 1,000 mg/kg of YKS had no effect on orexin levels. Therefore, 300 mg/kg of YKS was an effective dose for controlling orexin secretion. Subsequently, rats were divided into group-housed control (Con), individually housed stress (Stress), and individually housed YKS (300 mg/kg)-treated stress (Stress + YKS) groups. After 1 week, a resident-intruder aggression test was performed, and the plasma levels of orexin and corticosterone were measured. In the Stress group, aggressive behavior and the levels of corticosterone and orexin significantly increased compared with the Con group; however, these effects were inhibited in the Stress + YKS group. Further, an orexin receptor antagonist (TCS 1102; 10 mg/kg) was intraperitoneally administered to rats exposed to isolation stress to determine whether orexin was involved in stress responses. Under these conditions, aggressive behavior and the level of corticosterone significantly decreased compared with the Stress group.
  
  
  CONCLUSIONS
  These results suggest that orexin is involved in the control of stress response and that YKS exerts an antistress effect via the regulation of orexin secretion.
authors.affiliation: Department of Physiology.
authors.forename: Haruto
authors.initials: H
authors.lastname: Katahira
authors.affiliation: Department of Physiology.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sunagawa
authors.affiliation: Department of Physiology; Department of Neurology, School of Medicine, Showa University.
authors.forename: Daishi
authors.initials: D
authors.lastname: Watanabe
authors.affiliation: Department of Physiology; Department of Surgery, Showa University Koto Toyosu Hospital, Tokyo.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Kanada
authors.affiliation: Department of Physiology.
authors.forename: Ayami
authors.initials: A
authors.lastname: Katayama
authors.affiliation: Department of Physiology.
authors.forename: Risa
authors.initials: R
authors.lastname: Yamauchi
authors.affiliation: Department of Orthopaedic Surgery, Showa University Fujigaoka Hospital, Kanagawa, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Takashima
authors.affiliation: Department of Physiology.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ishikawa
authors.affiliation: Department of Physiology.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Hisamitsu
keywords: Yokukansan; aggressive behavior; antistress effect; corticosterone; orexin; social isolation stress