The effects of valproate and olanzapine on the abnormal behavior of diacylglycerol kinase β knockout mice.
The effects of valproate and olanzapine on the abnormal behavior of diacylglycerol kinase β knockout mice.
复制标题
丙戊酸钠和奥氮平对二酰甘油激酶β基因敲除小鼠异常行为的影响。
DOI：
10.1016/j.pharep.2014.10.009
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发表时间：
2015
影响因子：
4.4
通讯作者：
Shimazawa M. and Hara H.
中科院分区：
文献类型：
--
作者：
Ishisaka M.;Tsujii S.;Mizoguchi T.; Tsuruma K.;Shimazawa M. and Hara H.
研究背景甘油二酯激酶（Diacylglycerol kinase，DGK）是一种将甘油二酯转化为磷脂酸的酶。之前，我们报道了DGKβ基因敲除（KO）小鼠表现出躁狂样行为，如多动，焦虑减少和认知障碍。此外，锂改善了DGKβ KO小鼠的多动性并降低了焦虑。本研究观察了抗躁狂药物丙戊酸钠和奥氮平对DGKβ KO小鼠异常行为的影响。药物治疗后，进行行为学测试，以研究小鼠的自主活动、焦虑水平和认知功能。结果丙戊酸盐和奥氮平单次治疗不能改善DGKβ KO小鼠的多动或异常焦虑水平。丙戊酸盐和奥氮平长期给药显著降低了DGKβ KO小鼠的自主活动和异常焦虑水平。结论DGK β KO小鼠的行为异常与抗躁狂药物有关，DGK β KO小鼠可作为躁狂症的动物模型。
BackgroundDiacylglycerol 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.MethodsValproate (100 mg/kg/day) and olanzapine (1 mg/kg/day) were administered intraperitoneally. Following drugs treatments, behavioral tests were performed to investigate locomotor activity, anxiety levels, and cognitive function of the mice.ResultsA 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.ConclusionThese 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.