title: Brain region-specific reduction in c-Fos expression associated with an anxiolytic effect of yokukansan in rats.
abstract: BACKGROUND
  A traditional Japanese (Kampo) medicine, yokukansan, has long been used to treat neurosis, insomnia, and night crying and irritability in children. Recently, this medicine has reported to improve the behavioral and psychological symptoms of dementia that often become problematic in patients with Alzheimer's disease and other forms of dementia.
  
  
  OBJECTIVE
  Several animal studies have reported that yokukansan has an anxiolytic effect. However, the underlying mechanisms are not yet understood. In the present study, we investigated the effects in rats of single and repeated administrations of yokukansan on anxiety-like behaviors, stress responses, and the brain regions involved.
  
  
  METHODS
  Yokukansan dissolved in water (100 or 300 mg/kg) was administered orally to F344/N male rats 1h before each test or for two weeks before the tests began. Locomotor activity and anxiety-related behavior in the open-field test and the elevated plus-maze test, serum corticosterone levels, and restraint stress-induced c-Fos expression in various brain regions as a marker of neuronal activation were evaluated in both the vehicle-treated and yokukansan-treated rats.
  
  
  RESULTS
  A single administration of yokukansan had no effect on locomotor activity or anxiety-like behavior; however, repeated administration decreased anxiety-like behavior in a dose-dependent manner. Neither single nor repeated administration of yokukansan had an effect on the basal or stress-induced levels of serum corticosterone. For c-Fos expression, restraint stress increased the number of c-Fos-positive cells in the subdivisions of the prefrontal cortex, amygdala, and hypothalamus. Repeated administration of yokukansan decreased the stress-induced c-Fos expression in the prelimbic cortex and the basolateral and medial amygdaloid nuclei.
  
  
  CONCLUSIONS
  The present study indicates that repeated oral administration of yokukansan has an anxiolytic effect and that this effect may be associated with attenuated neuronal activity in the medial prefrontal cortex and amygdala.
authors.affiliation: Section of Oriental Medicine, Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology (NCGG), 36-3 Gengo, Morioka, Obu, Aichi 474-8511, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Shoji
authors.forename: Kazushige
authors.initials: K
authors.lastname: Mizoguchi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D020834:Ethnopharmacology; D007564:Japan; D008297:Male; D020835:Medicine, Kampo; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D014151:Anti-Anxiety Agents; D004365:Drugs, Chinese Herbal; D016760:Proto-Oncogene Proteins c-fos; C524644:Yi-Gan San
keywords: Anxiolytic effect; Kampo medicine; Rat; Restraint stress; Yokukansan; c-Fos