Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.
Chronic stress disrupts fear extinction and enhances amygdala and hippocampal Fos expression in an animal model of post-traumatic stress disorder.
复制标题
DOI：
10.1016/j.nlm.2014.01.018
复制
发表时间：
2014-07
影响因子：
2.7
通讯作者：
Conrad CD
中科院分区：
文献类型：
--
作者：
Hoffman AN;Lorson NG;Sanabria F;Foster Olive M;Conrad CD
慢性压力可能会导致在创伤事件后出现适应不良的恐惧相关行为。尽管之前的研究发现，慢性压力会损害已消除的恐惧的获得和回忆，但目前尚不清楚慢性压力如何影响非联想恐惧，例如在没有条件刺激（CS）的情况下或在新的环境中。雄性大鼠受到慢性应激（STR；钢丝网约束 6 小时/天/21 天）或不受干扰（CON），然后在相同环境下测试恐惧获得（3 种音调-足部电击配对）和两次消退阶段（15 种音调/阶段）。然后，每组在相同的环境 (SAME) 或新的环境 (NOVEL) 中进行测试（6 个音调），并使用 Fos 免疫组织化学对大脑进行功能激活处理。与 CON 相比，STR 显示出促进恐惧习得、在第一个灭绝日抵抗 CS 灭绝、以及在第二个灭绝日恐惧反应的强劲恢复。与 CON 相比，STR 在第一个灭绝日也表现出对环境的强烈冻结。当在相同或新的环境中进行测试时，STR 表现出比 CON 更高的对环境的冻结，这表明 STR 引起的恐惧与环境无关。为了支持这一点，STR 显示在 SAME 和 NOVEL 环境中，基底外侧杏仁核和海马 CA1 区域的 Fos 样表达增加。在 STR-NOVEL 与 CON-NOVEL 中，在中央杏仁核中也观察到 Fos 样表达增加。这些数据表明，慢性压力会增强恐惧学习并损害消退，并影响非联想过程，正如在新环境中增强的恐惧所证明的那样。
Chronic stress may impose a vulnerability to develop maladaptive fear-related behaviors after a traumatic event. Whereas previous work found that chronic stress impairs the acquisition and recall of extinguished fear, it is unknown how chronic stress impacts nonassociative fear, such as in the absence of the conditioned stimulus (CS) or in a novel context. Male rats were subjected to chronic stress (STR; wire mesh restraint 6h/d/21d) or undisturbed (CON), then tested on fear acquisition (3 tone-footshock pairings), and two extinction sessions (15 tones/session) within the same context. Then each group was tested (6 tones) in the same context (SAME) or a novel context (NOVEL), and brains were processed for functional activation using Fos immunohistochemistry. Compared to CON, STR showed facilitated fear acquisition, resistance to CS extinction on the first extinction day, and robust recovery of fear responses on the second extinction day. STR also showed robust freezing to the context alone during the first extinction day compared to CON. When tested in the same or a novel context, STR exhibited higher freezing to context than did CON, suggesting that STR-induced fear was independent of context. In support of this, STR showed increased Fos-like expression in the basolateral amygdala and CA1 region of the hippocampus in both the SAME and NOVEL contexts. Increased Fos-like expression was also observed in the central amygdala in STR-NOVEL vs. CON-NOVEL. These data demonstrate that chronic stress enhances fear learning and impairs extinction, and affects nonassociative processes as demonstrated by enhanced fear in a novel context.
登录
查看更多内容
影响因子：
2
作者：
Knapska, Ewelina;Maren, Stephen
通讯作者：
Maren, Stephen
影响因子：
10.6
作者：
Liberzon, I;Taylor, SF;Fig, LM
通讯作者：
Fig, LM
影响因子：
3.1
作者：
Kessler, Ronald C.;Petukhova, Maria;Sampson, Nancy A.;Zaslavsky, Alan M.;Wittchen, Hans-Ullrich
通讯作者：
Wittchen, Hans-Ullrich
影响因子：
2.7
作者：
Bellani, R;Luecken, LJ;Conrad, CD
通讯作者：
Conrad, CD
影响因子：
2.7
作者：
Huynh, Thu N.;Krigbaum, Amanda M.;Conrad, Cheryl D.
通讯作者：
Conrad, Cheryl D.