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. CONCLUSION: 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.