title: Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear.
abstract: 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.
authors.affiliation: Department of Neurology, Kunming Affiliated Hospital of Dali University, Kunming, 650011, China; Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China; Department of Neuropsychopathy, Clinical Medical School, Dali University, Dali, 671000, China.
authors.forename: Lizhu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Rongrong
authors.initials: R
authors.lastname: Mao
authors.affiliation: The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
authors.forename: Jianbin
authors.initials: J
authors.lastname: Tong
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Jinnan
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Anping
authors.initials: A
authors.lastname: Chai
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Qixin
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Yuexiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Mental Health Institute, The 2nd Xiangya Hospital, and Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, 410011, China. Electronic address: llj2920@163.com.
authors.forename: Lingjiang
authors.initials: L
authors.lastname: Li
authors.affiliation: Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China; Mental Health Institute, The 2nd Xiangya Hospital, and Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, 410011, China; University of the Chinese Academy of Sciences, Beijing, 100049, China. Electronic address: lxu@vip.163.com.
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
mesh_terms: D000634:Aminoquinolines / Q000008:administration & dosage*; D000818:Animals; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology* / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D011743:Pyrimidines / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors* / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; C487513:NSC 23766; D011743:Pyrimidines; C499134:Rac1 protein, rat; D020830:rac1 GTP-Binding Protein
keywords: Contextual fear memory; Extinction; Hippocampus; Rac1 activity