Treatment resistance of anxiety-related disorders often arises from an inappropriate fear expression, impairment in fear extinction, and spontaneous return of fear. Stress exposure is considered a high risk factor for neuropsychiatric disorders, but understanding of the long-term consequences of stress is limited, particularly when it comes to treatment outcome. Therefore, studying the consequences of acute stress would provide critical information on the role of stress in psychopathology. In the present study, we investigated the effect of acute immobilization stress on anxiety-like behavior and on conditioned fear memory. Our results demonstrate that prior stress exposure had no effect on anxiety-related behavior, fear acquisition, as well as fear extinction compared to non-stressed controls, but resulted in significantly higher rates of freezing during recall of extinction, indicating a consolidation failure. Further, immunohistochemical analysis of the expression of the immediate early gene c-Fos after recall of extinction revealed increased neuronal activity in the posterior paraventricular nucleus of the thalamus (PVT) in previously stressed animals compared to non-stressed controls. These results indicate, firstly, that acute stress affects long-term fear memory even after successful extinction training, and secondly, a strong involvement of the PVT in maladaptive fear responses induced by prior stress. Thus, stress-induced changes in PVT neuronal activity might be of importance for the pathophysiology of stress-sensitive anxiety-related psychiatric disorders, since exposure to an earlier acute stressor could counteract the success of therapy.

焦虑相关疾病的治疗抵抗通常源于不适当的恐惧表达、恐惧消退障碍以及恐惧的自发回归。压力暴露被认为是神经精神疾病的高危因素，但对压力的长期后果的了解有限，特别是在治疗结果方面。因此，研究急性压力的后果将为压力在精神病理学中的作用提供重要信息。在本研究中，我们研究了急性固定应激对焦虑样行为和条件性恐惧记忆的影响。我们的结果表明，与无压力的对照组相比，先前的压力暴露对焦虑相关行为、恐惧获得和恐惧消退没有影响，但会导致回忆消退过程中的冻结率显着升高，表明巩固失败。此外，对记忆灭绝后立即早期基因 c-Fos 表达的免疫组织化学分析显示，与未应激的对照组相比，先前应激的动物丘脑后室旁核 (PVT) 的神经元活动增加。这些结果首先表明，即使在成功的消退训练之后，急性压力也会影响长期的恐惧记忆；其次，PVT 强烈参与先前压力引起的适应不良的恐惧反应。因此，压力引起的 PVT 神经元活动变化可能对于压力敏感的焦虑相关精神疾病的病理生理学很重要，因为暴露于早期的急性压力源可能会抵消治疗的成功。