Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear
Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear
复制标题
海马区 Rac1 活性的抑制会损害情境恐惧的消退
DOI：
10.1016/j.neuropharm.2016.06.017
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发表时间：
2016-10-01
影响因子：
4.7
通讯作者：
Xu, Lin
中科院分区：
文献类型：
--
作者：
Jiang, Lizhu;Mao, Rongrong;Xu, Lin
促进恐惧记忆消退是治疗恐惧障碍，特别是创伤后应激障碍（PTSD）的主要方法。然而，这些患者的恐惧消退往往是不完全的。我们的前期研究表明，大鼠海马Rac 1的活性在情境恐惧记忆的学习中起着至关重要的作用。在这里，我们进一步研究了Rac1活动是否也调制了背景恐惧记忆的消退。我们发现，集体消退明显上调海马Rac 1活性，并诱导大鼠长期的背景恐惧消退。海马内注射Rac1抑制剂NSC23766可防止大规模消退训练大鼠的背景恐惧消退。相比之下，长间隔灭绝下调Rac1活性，导致较少的灭绝。Rac1激活剂CN04-A促进长间隔灭绝大鼠的背景恐惧消退。我们的研究表明，抑制Rac1活性在海马损害灭绝的背景恐惧，这表明，调节Rac1活性的海马可能是有前途的治疗恐惧障碍。(C)2016爱思唯尔有限公司版权所有
Promoting extinction of fear memory is the main treatment of fear disorders, especially post-traumatic stress disorder (PTSD). However, fear extinction is often incomplete in these patients. Our previous study had shown that Rac1 activity in hippocampus plays a crucial role in the learning of contextual fear memory in rats. Here, we further investigated whether Rac1 activity also modulated the extinction of contextual fear memory. We found that massed extinction obviously upregulated hippocampal Rac1 activity and induced long-term extinction of contextual fear in rats. Intrahippocampal injection of the Rac1 inhibitor NSC23766 prevents extinction of contextual fear in massed extinction training rats. In contrast, long-spaced extinction downregulated Rac1 activity and caused less extinction. And Rac1 activator CN04-A promotes extinction of contextual fear in long-spaced extinction rats. Our study demonstrates that inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear, suggesting that modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders. (C) 2016 Elsevier Ltd. All rights reserved.