Reznikov Roman, Diwan Mustansir, Nobrega José N, Hamani Clement
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada; Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
Research Imaging Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON, M5T 1R8, Canada.
J Psychiatr Res. 2015 Feb;61:158-65. doi: 10.1016/j.jpsychires.2014.12.017. Epub 2014 Dec 26.
Most of the available preclinical models of PTSD have focused on isolated behavioural aspects and have not considered individual variations in response to stress. We employed behavioural criteria to identify and characterize a subpopulation of rats that present several features analogous to PTSD-like states after exposure to classical fear conditioning. Outbred Sprague-Dawley rats were segregated into weak- and strong-extinction groups on the basis of behavioural scores during extinction of conditioned fear responses. Animals were subsequently tested for anxiety-like behaviour in the open-field test (OFT), novelty suppressed feeding (NSF) and elevated plus maze (EPM). Baseline plasma corticosterone was measured prior to any behavioural manipulation. In a second experiment, rats underwent OFT, NSF and EPM prior to being subjected to fear conditioning to ascertain whether or not pre-stress levels of anxiety-like behaviours could predict extinction scores. We found that 25% of rats exhibit low extinction rates of conditioned fear, a feature that was associated with increased anxiety-like behaviour across multiple tests in comparison to rats showing strong extinction. In addition, weak-extinction animals showed low levels of corticosterone prior to fear conditioning, a variable that seemed to predict extinction recall scores. In a separate experiment, anxiety measures taken prior to fear conditioning were not predictive of a weak-extinction phenotype, suggesting that weak-extinction animals do not show detectable traits of anxiety in the absence of a stressful experience. These findings suggest that extinction impairment may be used to identify stress-vulnerable rats, thus providing a useful model for elucidating mechanisms and investigating potential treatments for PTSD.
大多数现有的创伤后应激障碍（PTSD）临床前模型都集中在孤立的行为方面，没有考虑到个体对压力反应的差异。我们采用行为标准来识别和表征一组大鼠亚群，这些大鼠在经历经典恐惧条件反射后呈现出几种类似于创伤后应激障碍样状态的特征。将远交群斯普拉格-道利大鼠根据条件性恐惧反应消退期间的行为评分分为弱消退组和强消退组。随后在旷场试验（OFT）、新奇抑制摄食（NSF）和高架十字迷宫（EPM）中对动物进行焦虑样行为测试。在进行任何行为操作之前测量基线血浆皮质酮。在第二个实验中，大鼠在接受恐惧条件反射之前先进行OFT、NSF和EPM，以确定应激前焦虑样行为水平是否可以预测消退分数。我们发现25%的大鼠表现出条件性恐惧的低消退率，与表现出强消退的大鼠相比，这一特征与多项测试中焦虑样行为增加有关。此外，弱消退动物在恐惧条件反射之前皮质酮水平较低，这一变量似乎可以预测消退回忆分数。在另一个实验中，恐惧条件反射之前进行的焦虑测量不能预测弱消退表型，这表明弱消退动物在没有应激经历的情况下没有表现出可检测到的焦虑特征。这些发现表明，消退损伤可能用于识别应激易感性大鼠，从而为阐明机制和研究创伤后应激障碍的潜在治疗方法提供一个有用的模型。
