脂多糖免疫激活导致抑郁性行为的动物研究:剂量和时程效应
Animal Research on Immunity Activation-Induced Depressive-Like Behavior:Doses and Time Effects
查看参考文献22篇
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文摘
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"抑郁症细胞因子假说"的提出为抑郁障碍的病因学研究提供了一个新的方向,为了探讨脂多糖(lipopo-lysaccharide,LPS)诱导的免疫激活与抑郁性行为产生之间的关系,本研究采用50只SD大鼠随机分为五组LPS400,LPS200,LPS50,LPS10,LPS0,分别于实验期第0天和第3天注入LPS400μg/kg,200μg/kg,50μg/kg,10μg/kg和生理盐水。以糖精水偏爱,旷场行为和高架十字迷宫评定大鼠LPS注射后2h,24h,48h的行为变化。结果显示一次LPS注射后2h,LPS50,LPS200,LPS400组动物与生理盐水组动物相比较,其糖精水偏爱分数(p<0.01),旷场中的水平活动距离(p<0.01)和直立行为(p<0.01)以及高架十字迷宫中的闭合臂进入次数(p<0.01)和开放臂进入次数显著下降(p<0.01);重复注射后2hLPS注射组动物的闭合臂进入次数显著降低(p<0.01);但LPS10组与生理盐水组动物在行为上没有差异,50μg/kg,200μg/kg和400μg/kg剂量的各组之间没有差异。LPS注射后24h和48h以及重复注射后大鼠的行为没有发现显著变化。提示LPS诱导的免疫激活对抑郁行为产生有一定的作用。免疫激活的细胞因子能够导致动物出现明显的抑郁性行为,但是这种行为缺乏长时程效应,因此LPS诱导的抑郁障碍的动物模型应用是非常有限的。免疫激活的前炎性细胞因子可能是导致抑郁障碍产生的其中一个原因而不是唯一原因。 |
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其他语种文摘
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The "cytokine theory of depression" indicated that cytokines induced by immunity activity are not only immunity mediators but also play an important role in the mechanism of depressive-like behaviors. The administration of lipopolysaccharide (LPS), which is a product of the cell wall of Gram-negative bacteria, is known to activate immune functions and induce the release of several cytokines both in the periphery, and the brain such as frontal cortex, hippocampus, and hypothalamus that are considered to be the essential brain regions of depression. Many studies found that the administration of LPS could induce depressive-like behavior, such as a decrease in the preference of sweet milk, low locomotion, and anorexia. However, these researches only pay attention to short-term behavior effects; the effects of LPS administration on long-term behavior changes have not been clearly reported. To further understand the role of immunity activation-induced cytokines in depression, the purpose of the present study was to investigate the effects of repeated administration of LPS in different doses on behavior and the long-term behavior effects in rats. Fifty rats were randomly divided into 4 LPS groups (LPS 400, LPS 200, LPS 50, and LPS 10) and 1 saline control group (LPS 0); each group comprised ten rats. According to the groups, the rats were injected intraperitoneally with LPS 400 μg/kg, 200 μg/kg, 50 μg/kg, 10 μg/kg, and saline, respectively; they were injected again after 3 days. Two hours, 24 hours, and 48 hours after every injection, the rats were subjected to a saccharin preference test, an open-field test, and an elevated plus-maze test. The results indicated that 2 hours after the first LPS injection, the percent of saccharin preference, locomotion and upright activity in the open-field test, and open arms and closed arms entries in the elevated plus-maze test were significantly lower in LPS 50, LPS 200, and LPS 400 than in the saline control group (percent of saccharin preference: p< 0.01; locomotion: p< 0.01; upright activity: p< 0.01; open arms entries: p< 0.01; and closed arms entries: p< 0.01). It was also found that the LPS-treated rats had fewer open arms entries than the saline controls 2 hours after the repeated LPS injection (p< 0.01). However, there was no significant difference between the LPS-treated groups and the saline control group with respect to behavior changes 24 hours and 48 hours after the first LPS injection and after the repeated LPS injection. In addition, there were no differences among LPS 400, LPS 200, and LPS 50 at any given point of time. Our results demonstrate that LPS-induced immunity activation can result in evident depressive-like behavior in animals. However, no significant long-term effect in behavior was found. Thus, the present results suggest that LPS-induced proinflammation cytokines may be one of the conditions, but not the only condition or sufficient condition that causes the long-term depression. Using the animal model of LPS-induced depression has certain limitations. |
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来源
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心理学报
,2007,39(6):1041-1047 【核心库】
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关键词
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脂多糖
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抑郁样行为
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快感缺乏
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自主活动
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地址
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中国科学院心理研究所脑—行为研究中心, 北京, 100101
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语种
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中文 |
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ISSN
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0439-755X |
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学科
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社会科学总论 |
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基金
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国家自然科学基金
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文献收藏号
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CSCD:3134857
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