Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear

被引：20

作者：

Jiang, Lizhu ^{[1
,2
,7
]}

Mao, Rongrong ^{[2
]}

Tong, Jianbin ^{[3
]}

Li, Jinnan ^{[2
]}

Chai, Anping ^{[2
]}

Zhou, Qixin ^{[2
]}

Yang, Yuexiong ^{[2
]}

Wang, Liping ^{[2
]}

Li, Lingjiang ^{[4
,5
]}

Xu, Lin ^{[2
,4
,5
,6
]}

机构：

[1] Dali Univ, Kunming Affiliated Hosp, Dept Neurol, Kunming 650011, Peoples R China

[2] Chinese Acad Sci, Kunming Inst Zool, Key Lab Anim Models & Human Dis Mechanisms, Kunming 650223, Peoples R China

[3] Cent South Univ, Xiangya Hosp 3, Changsha 410013, Hunan, Peoples R China

[4] Cent South Univ, Xiangya Hosp 2, Mental Hlth Inst, 132 Ren Ming Rd, Changsha 410011, Hunan, Peoples R China

[5] Cent South Univ, Key Lab Psychiat & Mental Hlth Hunan Prov, 132 Ren Ming Rd, Changsha 410011, Hunan, Peoples R China

[6] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[7] Dali Univ, Sch Clin Med, Dept Neuropsychopathy, Dali 671000, Peoples R China

来源：

NEUROPHARMACOLOGY | 2016年 / 109卷

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

Rac1; activity; Hippocampus; Extinction; Contextual fear memory; POSTTRAUMATIC-STRESS-DISORDER; DENDRITIC SPINES; CONDITIONAL FEAR; RHO-GTPASES; MAINTENANCE; RENEWAL;

D O I：

10.1016/j.neuropharm.2016.06.017

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：216 / 222

页数：7

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