GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice

GABAergic and nitriergic modulation by curcumin for its antianxiety-like activity in mice
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DOI:
10.1016/j.brainres.2010.07.007
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发表时间:
2010-09-17
期刊:
影响因子:
2.9
通讯作者:
Dhingra, Dinesh
Dhingra, Dinesh
中科院分区:
医学3区
文献类型:
--
作者:
Gilhotra, Neeraj;Dhingra, Dinesh

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本研究以姜黄有效成分姜黄素(10和20 mg/kg)对固定受限应激小鼠抗焦虑样活性的影响为研究对象,采用升高+迷宫实验、野外实验、明暗实验和社会互动实验评价其对焦虑的影响。只有较高剂量(20 mg/kg, i.p.)的姜黄素对应激小鼠产生显著的抗焦虑样作用。与姜黄素和氨基胍本身相比,诱导型一氧化氮合酶抑制剂氨基胍(50 mg/kg; i.p)预处理显著增强了应激小鼠中姜黄素的抗焦虑样作用。与姜黄素本身相比,神经元型一氧化氮合酶抑制剂7-硝基茚唑(20 mg/kg)预处理对应激小鼠姜黄素的抗焦虑样反应没有显著影响。约束应激显著增加小鼠血浆亚硝酸盐水平。姜黄素(20 mg/kg, ig)和氨基胍显著降低应激小鼠血浆亚硝酸盐水平。与姜黄素和氨基胍本身相比,氨基胍和姜黄素的组合显著降低了应激小鼠血浆亚硝酸盐水平。姜黄素和氨基胍对小鼠脑组织GABA含量无显著影响。地西泮(2 mg/kg)仅对非应激小鼠有明显的类焦虑作用,对应激小鼠无明显的解焦虑作用。然而,与各自的对照组相比,地西泮显著增加了非应激和应激小鼠的GABA含量。这些结果提示姜黄素的抗焦虑样作用可能只与诱导型NOS有关,而与神经元NOS无关。(C) 2010 Elsevier B.V.版权所有
In the present study, effect of curcumin (10 and 20 mg/kg), an active constituent of Curcuma longa was evaluated for its antianxiety-like activity in mice subjected to immobilization-induced restraint stress for 6 h. The effect on anxiety was assessed by employing elevated plus maze, open field test, light/dark test and social interaction test. Only the higher dose (20 mg/kg, i.p.) of curcumin produced significant antianxiety-like effect in stressed mice. Pre-treatment with aminoguanidine (50 mg/kg; i.p.), an inducible nitric oxide synthase inhibitor significantly enhanced the anxiolytic-like effect of curcumin in stressed mice as compared to curcumin and aminoguanidine per se in stressed mice. Pretreatment with 7-nitroindazole (20 mg/kg), a neuronal nitric oxide synthase inhibitor did not significantly affect the antianxiety-like response of curcumin in stressed mice as compared to curcumin per se. Restraint stress significantly increased plasma nitrite levels in mice. Curcumin (20 mg/kg, i.p.) and aminoguanidine significantly decreased plasma nitrite levels in stressed mice. The combination of aminoguanidine and curcumin significantly decreased the plasma nitrite levels as compared to curcumin and aminoguanidine per se in stressed mice. Curcumin and aminoguanidine did not produce any significant change in brain GABA contents of the animals. Diazepam (2 mg/kg) produced significant anxiolytic-like effect only in unstressed mice, but could not exert significant anxiolysis in stressed mice. However, diazepam significantly increased GABA contents in both unstressed and stressed mice as compared to respective control groups. These findings suggest the possible involvement of only inducible NOS and not neuronal NOS in antianxiety-like effect of curcumin. (C) 2010 Elsevier B.V. All rights reserved.