Inhibition of Rac1 activity in the hippocampus impaired extinction of contextual fear. (October 2016)

• Record Type: Journal Article
• Authors: Jiang, Lizhu; Mao, Rongrong; Tong, Jianbin; Li, Jinnan; Chai, Anping; Zhou, Qixin; Yang, Yuexiong; Wang, Liping; Li, Lingjiang; Xu, Lin
• Is Part Of: Neuropharmacology. Volume 109(2016)
• Page Start: 216
• Page End: 222
• Publication Date: 2016-10
• Subjects: Rac1 activity -- Hippocampus -- Extinction -- Contextual fear memory; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2016.06.017
• Languages: English
• ISSNs: 0028-3908

Abstract

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. Highlights: Rac1 is involved in dendritic remodeling and hippocampus-dependent memory. Inhibition of hippocampal Rac1 activity impaired extinction, while activation of hippocampal Rac1 facilitated extinction. Modulating Rac1 activity of the hippocampus may be promising therapy of fear disorders.