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只有暴露于创伤后应激障碍模型的易感大鼠才会对创伤相关线索和其他症状产生反应:单次注射苯丙胺可消除这种效应。

Only susceptible rats exposed to a model of PTSD exhibit reactivity to trauma-related cues and other symptoms: an effect abolished by a single amphetamine injection.

作者信息

Toledano Daniel, Gisquet-Verrier Pascale

机构信息

CNRS, Centre de Neurosciences Paris-Sud, Université Paris-Sud, UMR 8195, F-91405 Orsay, France; Université Paris-Sud, UMR 8195, Orsay F-91405, France.

出版信息

Behav Brain Res. 2014 Oct 1;272:165-74. doi: 10.1016/j.bbr.2014.06.039. Epub 2014 Jun 27.

DOI:10.1016/j.bbr.2014.06.039
PMID:24975424
Abstract

The present study had two main goals. First, to investigate whether an animal model of post traumatic stress disorder (PTSD), single prolonged stress (SPS) leads to one of the main PTSD symptom: avoidance of trauma-related stimuli. Second, to investigate whether a single amphetamine injection delivered 30 days after SPS can reduce these symptoms. Olfactory and auditory cues were added to the SPS context and reactivity to these cues were tested more than one month later using an odor discrimination test, and freezing to the trauma-related tone. Other PTSD symptoms, such as anxiety (elevated plus maze) and hyperarousal (acoustic startle response), were also investigated in these rats. Some behavioural reactivity to the environmental cues was observed in rats exposed to SPS. However, a subgroup of these rats showed an exaggerated disruption in performance in 3 to 4 of the behavioral tests relative to controls, suggesting that two classes of rats, those that are susceptible and those that are resilient to SPS, can be dissociated. When rats were treated with amphetamine (1mg/kg) injected in the SPS context 30 days after SPS, traumatized rats no longer differed from their corresponding controls and all were identified as resilient. The present data demonstrated that rats exposed to SPS can be either susceptible or resilient and a single amphetamine injection can abolish the associated symptoms. We propose that combining memory reactivation, with an amphetamine-induced positive mood, can modify the emotional valence of the initial memory, inducing long-lasting remodeling of the traumatic memory, thereby opening a novel therapeutic avenue.

摘要

本研究有两个主要目标。第一,研究创伤后应激障碍(PTSD)的动物模型——单次长时间应激(SPS)是否会导致PTSD的主要症状之一:回避与创伤相关的刺激。第二,研究在SPS后30天注射一次苯丙胺是否能减轻这些症状。在SPS情境中加入嗅觉和听觉线索,并在一个多月后使用气味辨别测试以及对与创伤相关的音调产生僵住反应来测试对这些线索的反应性。还对这些大鼠的其他PTSD症状进行了研究,如焦虑(高架十字迷宫实验)和过度觉醒(听觉惊吓反应)。在暴露于SPS的大鼠中观察到了对环境线索的一些行为反应。然而,相对于对照组,这些大鼠中的一个亚组在3至4项行为测试中的表现出现了过度的破坏,这表明可以区分出两类大鼠,即对SPS敏感的大鼠和具有恢复力的大鼠。当在SPS后30天在SPS情境中给大鼠注射苯丙胺(1mg/kg)时,受过创伤的大鼠与相应的对照组不再有差异,并且所有大鼠都被确定为具有恢复力。目前的数据表明,暴露于SPS的大鼠可能敏感也可能具有恢复力,单次注射苯丙胺可以消除相关症状。我们提出,将记忆重新激活与苯丙胺诱导的积极情绪相结合,可以改变初始记忆的情感效价,诱导创伤性记忆的持久重塑,从而开辟一条新的治疗途径。

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