Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress
Lesions of the basolateral amygdala reverse the long-lasting interference with shuttle box escape produced by uncontrollable stress
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DOI：
10.1016/j.bbr.2010.03.012
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发表时间：
2010-07-29
影响因子：
2.7
通讯作者：
Fleshner, Monika
中科院分区：
文献类型：
--
作者：
Greenwood, Benjamin N.;Strong, Paul V.;Fleshner, Monika
暴露在无法控制但无法控制的压力源下会产生一系列称为习得性无助的行为。对于啮齿类动物来说，无法控制的压力会干扰学习逃离穿梭箱中可逃避的电击的能力。压力引起的穿梭盒逃逸缺陷是潜在抗抑郁策略的常见筛选工具。关于压力引起的逃避缺陷的时间进程和潜在机制，文献中存在不一致的地方。当压力源和测试环境之间没有共同的线索时，逃避缺陷是短暂的，并且与条件冻结无关。相反，当压力和测试发生在相同或相似的环境中时，逃避缺陷会非常持久。目前的研究提出了这样一个假设：无法控制的压力产生的长期逃避缺陷取决于条件性恐惧和基底外侧杏仁核（BLA）。在无法控制的足部电击后两周，大鼠双侧 BLA 出现兴奋性毒性损伤。手术后一周，在先前进行足部电击的同一穿梭箱中，对大鼠进行条件冻结和逃跑行为测试。具有假损伤的应激大鼠表现出强烈的条件冻结，并且在穿梭箱测试期间未能逃脱。 BLA 的损伤消除了条件性冷冻，并完全恢复了应激大鼠执行逃生应急措施的能力。这些数据表明，在压力源和测试环境共享共同线索的条件下产生的长期压力诱导的逃避缺陷取决于 BLA 引起的条件冻结。结果对习得性无助现象的机制具有重要意义。 (C) 2010 Elsevier B.V. 保留所有权利。
Exposure to an uncontrollable, but not a controllable, stressor produces a constellation of behaviors called learned helplessness. In rodents, uncontrollable stress interferes with the ability to learn to escape from escapable shocks delivered in a shuttle box. The stress-induced shuttle box escape deficit is a common screening tool for potential antidepressant strategies. Inconsistencies in the literature exist regarding the time-course of, and mechanisms underlying, stress-induced escape deficits. When no common cues are shared between the stressor and testing environment, the escape deficit is short lived and independent of conditioned freezing. In contrast, when stress and testing occur in the same or similar environments, the escape deficit is very long lasting. The current studies address the hypothesis that the long-lived escape deficit produced by uncontrollable stress is dependent upon conditioned fear and the basolateral amygdala (BLA). Rats received bilateral excitotoxic lesions of the BLA 2 weeks following uncontrollable foot shocks. One week after surgery, rats were tested for conditioned freezing and escape behavior in the same shuttle boxes in which prior foot shocks were delivered. Stressed rats with sham lesions displayed robust conditioned freezing and failed to escape during shuttle box testing. Lesions of the BLA eliminated conditioned freezing and completely restored stressed rats' ability to perform the escape contingency. These data indicate that the long-lived stress-induced escape deficit produced under conditions in which the stressor and testing environments share common cues is dependent upon conditioned freezing elicited by the BLA. Results have important implications for the mechanisms underlying learned helplessness phenomena. (C) 2010 Elsevier B.V. All rights reserved.