Tapias-Espinosa Carles, Kádár Elisabet, Segura-Torres Pilar
Autonomous University of Barcelona, Department of Psychobiology and Methodology of Life Sciences. Institute of Neurosciences. 08193 Bellaterra, Barcelona, Spain; Autonomous University of Barcelona, Department of Psychiatry and Forensic Medicine. Institute of Neurosciences. 08193 Bellaterra, Barcelona, Spain.
University of Girona, Department of Biology. 17071 Girona, Spain.
Behav Brain Res. 2018 Jan 15;336:59-66. doi: 10.1016/j.bbr.2017.08.025. Epub 2017 Aug 26.
Extinction-based therapies (EBT) are the psychological treatments of choice for certain anxiety disorders, such as post-traumatic stress disorder. However, some patients relapse and suffer spontaneous recovery (SR) of anxiety symptoms and persistence of avoidance behaviour, which underlines the need for improving EBT. In rats, recent evidence has highlighted the relevance of the temporal distribution of extinction sessions in reducing SR of auditory fear conditioning, although it has seldom been studied in procedures involving proactive avoidance responses, such as two-way active avoidance conditioning (TWAA). We examined whether the temporal distribution of two extinction sessions separated by 24h or 7days (contiguous versus spaced extinction paradigms, respectively), influences SR after 28days of a TWAA task. c-Fos expression, as a marker of neuronal activation, was also measured by immunohistochemistry 90min after the SR test in the amygdala and the medial prefrontal cortex. The temporal distribution of extinction sessions did not affect the degree of extinction learning. However, only the rats that underwent the 7-day spaced extinction paradigm maintained the level of extinction in the long term, showing no SR in TWAA. This behavioural finding was consistent with a greater number of c-Fos-labelled neurons in the infralimbic cortex in the 7-day group, and in the Lateral and Central nuclei of the amygdala in the 24-hour group. These findings show that a time-spaced extinction paradigm reduces the spontaneous recovery of active avoidance behaviour, and that this behavioural advantage appears to be related to the activation of the infralimbic cortex.
基于消退的疗法（EBT）是某些焦虑症（如创伤后应激障碍）的首选心理治疗方法。然而，一些患者会复发，并出现焦虑症状的自发恢复（SR）以及回避行为的持续存在，这突出了改进EBT的必要性。在大鼠中，最近的证据强调了消退训练的时间分布在减少听觉恐惧条件反射的SR方面的相关性，尽管在涉及主动回避反应的程序（如双向主动回避条件反射（TWAA））中很少进行研究。我们研究了间隔24小时或7天的两次消退训练的时间分布（分别为连续与间隔消退范式）是否会影响TWAA任务28天后的SR。作为神经元激活标记的c-Fos表达，也在SR测试后90分钟通过免疫组织化学在杏仁核和内侧前额叶皮层中进行了测量。消退训练的时间分布不影响消退学习的程度。然而，只有接受7天间隔消退范式的大鼠在长期内保持了消退水平，在TWAA中未表现出SR。这一行为学发现与7天组在边缘下皮层以及24小时组在杏仁核的外侧和中央核中更多的c-Fos标记神经元一致。这些发现表明，时间间隔的消退范式可减少主动回避行为的自发恢复，并且这种行为优势似乎与边缘下皮层的激活有关。
