Kososan, a standardized traditional Japanese herbal medicine, reverses sleep disturbance in socially isolated mice via GABAA-benzodiazepine receptor complex activation.

Abstract

PURPOSE:

Kososan (KSS), a traditional Japanese medicine with a distinct aroma, is clinically used to treat affective disorders but its antidepressant-like effect has not been thoroughly investigated. In this study, we investigated the effects of inhaled and orally administered KSS on sleep disturbances in socially isolated mice.

METHODS:

Four-weeks-old male ddy mice were housed either in social isolation or in groups for 4-6 weeks before the experiment. KSS was orally administered (0.5 or 1.0 g/kg) or inhaled (0.5, 1.0, or 2.5 g/0.125 m(3)) 60 min before pentobarbital administration. Stress levels in mice were evaluated by the duration of pentobarbital-induced sleeping time.

RESULTS:

Sleeping time was shorter in socially-isolated mice than in group-housed mice. Oral and inhaled KSS prolonged sleeping time in stressed mice, but had no effect on sleeping time of group-housed mice. Prolonged sleeping time after oral KSS was significantly inhibited (p<0.05) by bicuculline (3 mg/kg, i.p.), a GABAA antagonist, but not by flumazenil (3 mg/kg, i.p.), a selective benzodiazepine antagonist. Prolonged sleeping time after KSS inhalation was significantly inhibited (p<0.05) by flumazenil but not by bicuculline.

CONCLUSIONS:

Our findings suggest that KSS activates GABAA-benzodiazepine receptor complex and reverses shortened pentobarbital-induced sleep caused by social isolation.

• Authors: Naoko Koga, Takuji Yamaguchi, Keiko K Lee, Hiroyuki Kobayashi
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 21 Issue 5 Pg. 697-703 (Apr 15 2014) ISSN: 1618-095X [Electronic] Germany
• PMID: 24300331 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier GmbH. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• GABA-A Receptor Agonists
• GABA-A Receptor Antagonists
• koso-san
• Phenobarbital

Topics

• Administration, Inhalation
• Administration, Oral
• Animals
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• GABA-A Receptor Agonists (therapeutic use)
• GABA-A Receptor Antagonists
• Male
• Medicine, East Asian Traditional
• Mice
• Phenobarbital
• Phytotherapy (methods)
• Sleep (drug effects)
• Sleep Wake Disorders (drug therapy)
• Social Isolation