title: Yokukansan, a traditional Japanese herbal medicine, alleviates the emotional abnormality induced by maladaptation to stress in mice.
abstract: The aim of the present study was to examine the effect of yokukansan, a traditional Japanese herbal medicine that is composed of Atractylodis lanceae Rhizoma, Poria, Cnidii Rhizoma, Uncariae Uncis cum Ramulus, Angelicae Radix, Bupleuri Radix and Glycyrrhizae Radix, on the emotional abnormality induced by maladaptation to stress in mice. Mice were exposed to repeated restraint stress for 60 or 240 min/day for 14 days. From the 3rd day of stress exposure, mice were given yokukansan orally (p.o.) or the 5-HT1A receptor agonist flesinoxan intraperitoneally (i.p.) immediately after the daily exposure to restraint stress. After the final exposure to restraint stress, the emotionality of mice was evaluated using an automatic hole-board apparatus. A single exposure to restraint stress for 60 min induced a decrease in head-dipping behavior in the hole-board test. This emotional stress response disappeared in mice that had been exposed to repeated restraint stress for 60 min/day for 14 days, which confirmed the development of stress adaptation. In contrast, mice that were exposed to restraint stress for 240 min/day for 14 days did not develop this stress adaptation, and still showed a decrease in head-dipping behavior. The decreased emotionality observed in stress-maladaptive mice was significantly recovered by chronic treatment with yokukansan (1000 mg/kg, p.o.) as well as flesinoxan (0.25 and 0.5 mg/kg, i.p.) immediately after daily exposure to stress. These findings suggest that yokukansan may have a beneficial effect on stress adaptation and alleviate the emotional abnormality under conditions of excessive stress.
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan. Electronic address: mtsuji@iuhw.ac.jp.
authors.forename: Minoru
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Takeuchi
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Miyagawa
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Ishii
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Taro
authors.initials: T
authors.lastname: Imai
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Department of Pharmacology, School of Pharmacy, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan; Advanced Education and Research Center for Kampo Medicine, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi 324-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takeda
mesh_terms: D000223:Adaptation, Psychological; D000818:Animals; D004365:Drugs, Chinese Herbal / Q000494:pharmacology / Q000627:therapeutic use*; D019684:Magnoliopsida; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008517:Phytotherapy; D010879:Piperazines / Q000494:pharmacology; D055441:Poria; D012149:Restraint, Physical; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy* / Q000209:etiology
chemical_list: D004365:Drugs, Chinese Herbal; D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; C524644:Yi-Gan San; C056895:flesinoxan
keywords: Emotional behavior; Hole-board; Mouse; Restraint stress; Stress adaptation; Yokukansan