Jiang Lizhu, Mao Rongrong, Tong Jianbin, Li Jinnan, Chai Anping, Zhou Qixin, Yang Yuexiong, Wang Liping, Li Lingjiang, Xu Lin
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.
Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, 650223, China.
Neuropharmacology. 2016 Oct;109:216-222. doi: 10.1016/j.neuropharm.2016.06.017. Epub 2016 Jun 18.
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.
促进恐惧记忆的消退是恐惧障碍尤其是创伤后应激障碍（PTSD）的主要治疗方法。然而，这些患者的恐惧消退往往不完全。我们之前的研究表明，海马体中的Rac1活性在大鼠情境恐惧记忆的学习中起关键作用。在此，我们进一步研究Rac1活性是否也调节情境恐惧记忆的消退。我们发现，密集消退明显上调了大鼠海马体中的Rac1活性，并诱导了情境恐惧的长期消退。海马体内注射Rac1抑制剂NSC23766可阻止密集消退训练大鼠的情境恐惧消退。相反，长时程间隔消退下调了Rac1活性，导致消退较少。并且Rac1激活剂CN04-A促进长时程间隔消退大鼠的情境恐惧消退。我们的研究表明，抑制海马体中的Rac1活性会损害情境恐惧的消退，这表明调节海马体的Rac1活性可能是治疗恐惧障碍的一种有前景的疗法。
