title: The effects of valproate and olanzapine on the abnormal behavior of diacylglycerol kinase β knockout mice.
abstract: BACKGROUND
  Diacylglycerol kinase (DGK) is an enzyme that converts diacylglycerol to phosphatidic acid. Previously, we reported that DGKβ knockout (KO) mice showed mania-like behaviors such as hyperactivity, reduced anxiety, and cognitive impairment. Furthermore, lithium ameliorated the hyperactivity and reduced anxiety of DGKβ KO mice. In this study, we investigated the effects of the clinically active antimanic drugs valproate and olanzapine on the abnormal behaviors of DGKβ KO mice.
  
  
  METHODS
  Valproate (100mg/kg/day) and olanzapine (1mg/kg/day) were administered intraperitoneally. Following drugs treatments, behavioral tests were performed to investigate locomotor activity, anxiety levels, and cognitive function of the mice.
  
  
  RESULTS
  A single treatment of valproate and olanzapine did not ameliorate the hyperactivity or abnormal anxiety level of DGKβ KO mice. Chronic treatment with valproate and olanzapine significantly decreased locomotor activity and abnormal anxiety levels of DGKβ KO mice. Additionally, valproate also ameliorated cognitive function of DGKβ KO mice.
  
  
  CONCLUSIONS
  These results suggest that the abnormal behaviors of DGKβ KO mice is responsive to antimanic drugs, and that DGKβ KO mice are useful as an animal model of mania.
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Mitsue
authors.initials: M
authors.lastname: Ishisaka
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Tsujii
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Mizoguchi
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tsuruma
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.affiliation: Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D000818:Animals; D001007:Anxiety / Q000188:drug therapy* / Q000235:genetics; D001569:Benzodiazepines / Q000494:pharmacology / Q000627:therapeutic use*; D003072:Cognition Disorders / Q000188:drug therapy* / Q000235:genetics; D019852:Diacylglycerol Kinase / Q000172:deficiency* / Q000235:genetics*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D000077152:Olanzapine; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001569:Benzodiazepines; D014635:Valproic Acid; D019852:Diacylglycerol Kinase; D000077152:Olanzapine
keywords: Diacylglycerol kinase β; Mania; Olanzapine; Valproate