Hoffman Ann N, Lorson Nickolaus G, Sanabria Federico, Foster Olive M, Conrad Cheryl D
Department of Psychology, Arizona State University, Box 1104, Tempe, AZ 85287-1104, United States.
Department of Psychology, Arizona State University, Box 1104, Tempe, AZ 85287-1104, United States.
Neurobiol Learn Mem. 2014 Jul;112:139-47. doi: 10.1016/j.nlm.2014.01.018. Epub 2014 Feb 4.
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 6 h/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.
慢性应激可能使人在经历创伤性事件后更容易出现与恐惧相关的适应不良行为。尽管先前的研究发现慢性应激会损害消退恐惧的习得和回忆，但尚不清楚慢性应激如何影响非联想性恐惧，例如在没有条件刺激（CS）的情况下或在新环境中。将雄性大鼠分为慢性应激组（STR；采用金属丝网束缚6小时/天，共21天）或未受干扰组（CON），然后对其进行恐惧习得测试（3次音调-足部电击配对），并在同一环境中进行两次消退训练（每次训练15次音调）。然后，每组在相同环境（SAME）或新环境（NOVEL）中接受测试（6次音调），并使用Fos免疫组织化学方法对大脑进行功能激活处理。与CON组相比，STR组表现出恐惧习得加快、在首次消退训练日对CS消退的抵抗以及在第二次消退训练日恐惧反应的强烈恢复。与CON组相比，STR组在首次消退训练日单独对环境也表现出强烈的僵立反应。当在相同或新环境中进行测试时，STR组比CON组对环境表现出更高的僵立反应，这表明STR诱导的恐惧与环境无关。支持这一观点的是，在SAME和NOVEL环境中，STR组杏仁核基底外侧和海马CA1区域的Fos样表达均增加。在STR-NOVEL组与CON-NOVEL组相比，中央杏仁核中也观察到Fos样表达增加。这些数据表明，慢性应激会增强恐惧学习并损害消退，并影响非联想过程，如在新环境中增强的恐惧所证明的那样。
