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一种更新的动物模型,它捕捉了创伤后应激障碍(PTSD)的认知和情感特征。

An updated animal model capturing both the cognitive and emotional features of post-traumatic stress disorder (PTSD).

作者信息

Berardi Andrea, Trezza Viviana, Palmery Maura, Trabace Luigia, Cuomo Vincenzo, Campolongo Patrizia

机构信息

Department of Physiology and Pharmacology, Sapienza University of Rome Rome, Italy.

Department of Science, University of Roma Tre Rome, Italy.

出版信息

Front Behav Neurosci. 2014 Apr 29;8:142. doi: 10.3389/fnbeh.2014.00142. eCollection 2014.

Abstract

The new-released Diagnostic and Statistical Manual of Mental Disorders (DSM-5) defines post-traumatic stress disorder (PTSD) as a "trauma and stressor-related disorder". PTSD pathogenesis relies on paradoxical changes of emotional memory processing induced by the trauma exposure and associated with emotional dysfunction. Several animal models of PTSD have been validated and are currently used. Each one mimics a particular subset of the disorder with particular emphasis, mainly driven by the past classification of PTSD in the DSM-4, on the emotional features. In view of the recent update in the DSM-5, our aim was to develop, by using well-validated paradigms, a modified model of PTSD able to mimic at the same time both the cognitive and emotional features of the disease. We exposed male rats to either a piece of worn cat collar or to a series of inescapable footshocks paired with a PTSD risk factor, i.e., social isolation. Animals were subsequently re-exposed to the conditioned contexts at different time intervals in order to test memory retention for the stressors. In addition, footshock-exposed rats were tested in the elevated-plus-maze and social interaction tests. We found that rats exposed to a cat collar exhibited an acute fear response that did not lead to enduring memory retention. Conversely, footshock-exposed rats expressed a successful retention of the stressful experience at 1, 7, 14, 21 and 56 post-exposure days. Footshock-exposed rats displayed an anxious behavioral profile in the social interaction test and a significantly reduced locomotor activity in the elevated-plus-maze test. These dysfunctions were not observed when animals were socially housed, thus highlighting a social buffering effect in the development of the pathology. Our results underline the good validity of a footshock-based paradigm paired with social isolation as a PTSD animal model, able to mimic at the same time both some of the enduring cognitive and emotional facets of the pathology.

摘要

新发布的《精神疾病诊断与统计手册》(第五版)(DSM - 5)将创伤后应激障碍(PTSD)定义为一种“与创伤及应激源相关的障碍”。PTSD的发病机制依赖于创伤暴露所引发的、与情绪功能障碍相关的情绪记忆处理的反常变化。几种PTSD动物模型已得到验证且目前仍在使用。每一种模型都模仿了该障碍的特定子集,主要受DSM - 4中PTSD过去的分类影响,特别强调情绪特征。鉴于DSM - 5的最新更新,我们的目标是通过使用经过充分验证的范式,开发一种改良的PTSD模型,该模型能够同时模仿该疾病的认知和情绪特征。我们将雄性大鼠暴露于一条用过的猫项圈或一系列与PTSD风险因素(即社会隔离)配对的不可逃避的足部电击之下。随后,在不同时间间隔让动物再次暴露于条件化情境中,以测试对应激源的记忆保持情况。此外,对接受足部电击的大鼠进行高架十字迷宫试验和社交互动试验。我们发现,暴露于猫项圈的大鼠表现出急性恐惧反应,但并未导致持久的记忆保持。相反,接受足部电击的大鼠在暴露后第1、7、14、21和56天表现出对应激经历的成功记忆保持。接受足部电击的大鼠在社交互动试验中表现出焦虑行为特征,在高架十字迷宫试验中的运动活动显著减少。当动物群居时未观察到这些功能障碍,从而突出了社交缓冲在该病理发展中的作用。我们的结果强调了一种基于足部电击并伴有社会隔离的范式作为PTSD动物模型具有良好的有效性,该模型能够同时模仿该病理的一些持久的认知和情绪方面。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/388d/4010768/de4068fad740/fnbeh-08-00142-g0001.jpg

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