title: Extracts of kava (Piper methysticum) induce acute anxiolytic-like behavioral changes in mice.
abstract: BACKGROUND
  Kava has been used for centuries by Pacific Islanders for its tranquilizing and sedative effects. Recent clinical trials suggest that kava has therapeutic value for the treatment of anxiety. Demonstration of kava's anxiolytic effects in animals under controlled conditions would provide additional support for its clinical potential as an anxiolytic and would facilitate investigation of its mechanism(s) of action.
  
  
  OBJECTIVE
  This study systematically characterized the acute dosage-dependent anxiolytic and sedative effects of kava extract in well established quantitative murine behavioral assays and compared kava- and diazepam-induced behavioral changes.
  
  
  METHODS
  Various doses of an ethanolic extract of kava root or diazepam were administered intraperitoneally to BALB/cByJ inbred mice. Behavioral changes were measured in the mirrored chamber avoidance assay and elevated plus-maze assay. Reduced latency to enter and increased time spent in a normally avoided environment operationally defined anxiolysis. Sedation was defined by a significant decrease in locomotor activity in a circular arena.
  
  
  RESULTS
  Kava extract produced statistically significant dose-dependent anxiolytic-like behavioral changes in both assays of anxiolysis. ED(50) values for kava-induced increases in time spent inside the mirrored chamber and on the open arms of the plus maze were 125 mg/kg and 88 mg/kg, respectively. Kava extract also caused a profound decrease in locomotor activity (ED(50) of 172 mg/kg). Flumazenil, a competitive benzodiazepine receptor antagonist, blocked both the anxiolytic and sedative effects of diazepam, but had no effect on kava's behavioral actions.
  
  
  CONCLUSIONS
  Kava extracts produce significant murine anxiolytic-like behavioral changes and sedation that are not mediated through the benzodiazepine binding site on the GABA(A) receptor complex.
authors.affiliation: Department of Physiology, University of Oklahoma Health Sciences Center, PO Box 26901, Oklahoma City, OK 73190, USA. kennon-garrett@ouhsc.edu
authors.forename: Kennon M
authors.initials: KM
authors.lastname: Garrett
authors.forename: Garo
authors.initials: G
authors.lastname: Basmadjian
authors.forename: Ikhlas A
authors.initials: IA
authors.lastname: Khan
authors.forename: Brian T
authors.initials: BT
authors.lastname: Schaneberg
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Seale
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy* / Q000523:psychology; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005442:Flumazenil / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D020901:Kava / Q000737:chemistry*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D009043:Motor Activity / Q000187:drug effects*; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D058787:GABA-A Receptor Antagonists; D006993:Hypnotics and Sedatives; D010936:Plant Extracts; D005442:Flumazenil; D003975:Diazepam