The role of norepinephrine in differential response to stress in an animal model of posttraumatic stress disorder.
The role of norepinephrine in differential response to stress in an animal model of posttraumatic stress disorder.
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DOI：
10.1016/j.biopsych.2010.11.029
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发表时间：
2011-09-01
影响因子：
10.6
通讯作者：
Raskind, Murray A.
中科院分区：
文献类型：
--
作者：
Olson, Valerie G.;Rockett, Hannah R.;Reh, Rebecca K.;Redila, Van A.;Tran, Phuong M.;Venkov, Heli A.;DeFino, Mia C.;Hague, Chris;Peskind, Elaine R.;Szot, Patricia;Raskind, Murray A.
关键词：
创伤后应激障碍（PTSD）是一种流行的精神障碍，由暴露于极端的创伤应激而诱发。然而，大多数暴露于创伤应激的个体不会发展为PTSD，并且可能被认为具有心理弹性。涉及PTSD易感性或恢复力的神经回路尚不清楚，但临床证据表明去甲肾上腺素能系统发生了变化。通过将C57 BL/6小鼠暴露于单次电击（2 mA，10秒），然后在25天内暴露于6次1分钟的电击情景提醒，开发了一种称为创伤性经历与应激回忆（TERS）的PTSD动物模型。电击前和最后一次提醒后的声学惊吓反应（ASR）测试允许实验人员将电击小鼠分为两个队列：出现ASR大幅增加的小鼠（TERS易感小鼠）和没有出现这种情况的小鼠（TERS适应性小鼠）。PTSD的攻击性和社会行为相关性在TERS易感小鼠中增加，但在TERS弹性小鼠或对照小鼠中没有增加。应激相关脑区c-Fos表达的特征显示，与对照小鼠相比，TERS敏感和TERS弹性小鼠在游泳应激后显示出不同的脑激活。去甲肾上腺素能抑制性自身受体的药理学激活或突触后α1-肾上腺素受体的阻断使TERS易感小鼠的ASR、攻击性和社会互动正常化。与对照组小鼠相比，TERS-弹性，但不是TERS敏感，小鼠表现出降低的行为反应性去甲肾上腺素能自身受体阻滞剂的趋势。这些数据暗示去甲肾上腺素能系统作为一个可能的网站的病理，也许也适应性可塑性在创伤应激反应。
Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder precipitated by exposure to extreme traumatic stress. Yet, most individuals exposed to traumatic stress do not develop PTSD and may be considered psychologically resilient. The neural circuits involved in susceptibility or resiliency to PTSD remain unclear, but clinical evidence implicates changes in the noradrenergic system. An animal model of PTSD called Traumatic Experience with Reminders of Stress (TERS) was developed by exposing C57BL/6 mice to a single shock (2mA, 10sec) followed by exposure to six contextual1-minute reminders of the shock overa 25-dayperiod. Acoustic startle response (ASR) testing before the shock and after the last reminder allowed experimenters to separate the shocked mice into two cohorts: mice that developed a greatly increased ASR (TERS-susceptible mice) and mice that did not (TERS-resilient mice). Aggressive and social behavioral correlates of PTSD increased in TERS-susceptible mice but not in TERS-resilient mice or control mice. Characterization of c-Fos expression in stress-related brain regions revealed that TERS-susceptible and TERS-resilient mice displayed divergent brain activation following swim stress compared with control mice. Pharmacological activation of noradrenergic inhibitory autoreceptors or blockade of postsynaptic α1-adrenoreceptors normalized ASR, aggression, and social interaction in TERS-susceptible mice. The TERS-resilient, but not TERS-susceptible, mice showed a trend toward decreased behavioral responsiveness to noradrenergic autoreceptor blockade compared with control mice. These data implicate the noradrenergic system as a possible site of pathological and perhaps also adaptive plasticity in response to traumatic stress.
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影响因子：
56.9
作者：
Olson, VG;Heusner, CL;Palmiter, RD
通讯作者：
Palmiter, RD
在大鼠和人类中持续的恐惧：恐惧与焦虑中的杏仁核的作用。
DOI：
10.1038/npp.2009.109
发表时间：
2010-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
--
作者：
通讯作者：
--
影响因子：
10.6
作者：
Morgan, CA;Wang, S;Charney, DS
通讯作者：
Charney, DS
影响因子：
1.9
作者：
Boehnlein, James K;Kinzie, J David
通讯作者：
Kinzie, J David
影响因子：
17.7
作者：
Geracioti, TD;Baker, DG;Kasckow, JW
通讯作者：
Kasckow, JW