Vulnerability to mild predator stress in serotonin transporter knockout mice

Vulnerability to mild predator stress in serotonin transporter knockout mice
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DOI:
10.1016/j.bbr.2006.02.012
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发表时间:
2006-06-03
影响因子:
2.7
通讯作者:
Holmes, Andrew
Holmes, Andrew
中科院分区:
心理学3区
文献类型:
--
作者:
Adamec, Robert;Burton, Paul;Holmes, Andrew

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捕食者应激对大鼠和小鼠焦虑样行为的影响可能是创伤后应激障碍(PTSD)的模型。单次猫暴露野生型(C57,CFW)小鼠可在高架加迷宫、明/暗盒子测试和惊吓中产生持久的焦虑样效应。此外,雌性而不是雄性C57小鼠在加号迷宫中因单独暴露于捕食者气味而变得更加焦虑,这表明它们对不同强度的捕食者应激源的脆弱性不同。在人类中,5-羟色胺(5-羟色胺)转运体(SERT)的遗传变异与焦虑之间存在联系。这促使了SERT基因敲除小鼠的产生[参见Holmes A,Murphy DL,Crawley JN。《生物精神病学》2003;54(10):953-9]。目前的研究使用这些小鼠来确定对捕食者气味的焦虑效应的脆弱性与5-羟色胺再摄取终身减少所导致的5-羟色胺传递异常之间是否存在联系。将野生型(WT,C57背景)、杂合子(SERT+/-,HET)和纯合子(SERT-/-,KO)小鼠分为处理对照组和暴露在充满猫气味的大型测试室10分钟的对照组。在接触或暴露在室内一周后,焦虑测试在明/暗周期的黑暗阶段进行,在红灯下进行。在SERT-/-小鼠的正迷宫和明/暗盒测试中,捕食者气味暴露有选择性地引起焦虑。暴露在捕食者气味中并没有加强惊吓。研究结果表明,5-羟色胺传递的异常在易受物种相关应激源的一些持久焦虑效应的易感性中起作用,并可能在易受创伤后应激障碍的易感性中发挥作用。(C)2006爱思唯尔B.V.保留所有权利。
Effect of predator stress on rat and mouse anxiety-like behavior may model aspects of post traumatic stress disorder (PTSD). A single cat exposure of wild type (C57, CFW) mice can produce lasting anxiety-like effects in the elevated plus maze, light/dark box tests and startle. In addition, female but not male C57 mice are made more anxious in the plus maze by exposure to predator odors alone, suggesting differential vulnerability to predator stressors of differing intensity. There is a link between genetic variation in the serotonin (5-HT) transporter (SERT) and anxiety in humans. This prompted the generation of SERT knockout mice [see Holmes A, Murphy DL, Crawley JN. Biol Psychiatry 2003;54(10):953-9]. Present work used these mice to determine if there was a link between vulnerability to the anxiogenic effects of predator odors and abnormalities of 5-HT transmission induced by a life long reduction in 5-HT reuptake. Wild type (WT, C57 background), heterozygous (SERT +/-, HET) mice and homozygous knockout (SERT -/-, KO) were assigned to handled control groups or groups exposed for 10 min to a large testing room rich in cat odor. One week after handling or room exposure, anxiety testing took place in the dark phase of the light/dark cycle, in red light. Predator odor exposure was selectively anxiogenic in the plus maze and light/dark box tests in SERT -/- mice. Exposure to predator odor did not potentiate startle. Findings suggest a role for abnormalities in 5-HT transmission in vulnerability to some of the lasting anxiogenic effects of species relevant stressors and possibly in vulnerability to PTSD. (c) 2006 Elsevier B.V All rights reserved.