Anti-PTSD Effects of Hypidone Hydrochloride (YL-0919): A Novel Combined Selective 5-HT Reuptake Inhibitor/5-HT(1A) Receptor Partial Agonist/5-HT(6) Receptor Full Agonist.
Anti-PTSD Effects of Hypidone Hydrochloride (YL-0919): A Novel Combined Selective 5-HT Reuptake Inhibitor/5-HT(1A) Receptor Partial Agonist/5-HT(6) Receptor Full Agonist.
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盐酸乙二酮 (YL-0919) 的抗 PTSD 作用：一种新型组合选择性 5-HT 再摄取抑制剂/5-HT1A 受体部分激动剂/5-HT6 受体完全激动剂
DOI：
10.3389/fphar.2021.625547
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发表时间：
2021
影响因子：
5.6
通讯作者：
Cao JB
中科院分区：
文献类型：
--
作者：
Liu WG;Zhang LM;Yao JQ;Yin YY;Zhang XY;Li YF;Cao JB
创伤后应激障碍（PTSD）是一种使人衰弱的创伤和应激相关的障碍，已成为一个主要的神经精神问题，导致个人健康和社会成本的实质性破坏。本课题组前期研究表明，新型选择性5-HT再摄取抑制剂/5-HT 1A受体部分激动剂/5-HT 6受体完全激动剂盐酸哈立酮（YL-0919）具有显著的抗抑郁、抗焦虑及促认知作用。然而，YL-0919是否具有抗PTSD作用及其机制尚不清楚。在本研究中，我们发现，YL-0919重复治疗可显著抑制大鼠中时间依赖性致敏（TDS）程序和PTSD小鼠模型中不可避免的电击足引起的背景恐惧、增强的焦虑和认知功能障碍。此外，我们发现用YL-0919重复处理显著逆转了伴随的脑源性神经营养因子（BDNF）和突触蛋白（synapsin 1和GluA 1）表达的降低，并改善了前额叶皮层（PFC）中的神经可塑性破坏，包括锥体神经元的树突复杂性和棘密度。综上所述，目前的研究表明，YL-0919具有明显的抗PTSD作用，这可能部分通过增加PFC中BDNF的表达和突触蛋白的形成来改善结构神经可塑性而介导。
Posttraumatic stress disorder (PTSD) is a debilitating trauma and stressor-related disorder that has become a major neuropsychiatric problem, leading to substantial disruptions in individual health and societal costs. Our previous studies have demonstrated that hypidone hydrochloride (YL-0919), a novel combined selective 5-HT reuptake inhibitor/5-HT1A receptor partial agonist/5-HT6 receptor full agonist, exerts notable antidepressant- and anxiolytic-like as well as procognitive effects. However, whether YL-0919 exerts anti-PTSD effects and its underlying mechanisms are still unclear. In the present study, we showed that repeated treatment with YL-0919 caused significant suppression of contextual fear, enhanced anxiety and cognitive dysfunction induced by the time-dependent sensitization (TDS) procedure in rats and by inescapable electric foot-shock in a mouse model of PTSD. Furthermore, we found that repeated treatment with YL-0919 significantly reversed the accompanying decreased expression of the brain-derived neurotrophic factor (BDNF) and the synaptic proteins (synapsin1 and GluA1), and ameliorated the neuroplasticity disruption in the prefrontal cortex (PFC), including the dendritic complexity and spine density of pyramidal neurons. Taken together, the current study indicated that YL-0919 exerts clear anti-PTSD effects, which might be partially mediated by ameliorating the structural neuroplasticity by increasing the expression of BDNF and the formation of synaptic proteins in the PFC.
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影响因子：
3.2
作者：
Homberg JR
通讯作者：
Homberg JR
DOI：
10.1073/pnas.95.24.14476
发表时间：
1998-11-24
影响因子：
11.1
作者：
Ramboz, S;Oosting, R;Hen, R
通讯作者：
Hen, R
影响因子：
2.7
作者：
de Lima, MNM;Laranja, DC;Schröder, N
通讯作者：
Schröder, N
中枢血清素缺乏小鼠的情境恐惧记忆增强
DOI：
10.1073/pnas.0801329105
发表时间：
2008-08-19
影响因子：
11.1
作者：
Dai, Jin-Xia;Han, Hui-Li;Xu, Lin
通讯作者：
Xu, Lin
YL-0919 的抗抑郁样活性：一种新型选择性血清素再摄取抑制剂和 5-HT1A 受体激动剂的组合
影响因子：
3.7
作者：
Chen HX;Jin ZL;Zhang LM;Xue R;Xu XD;Zhao N;Qiu ZK;Wang XW;Zhang YZ;Yang RF;Li YF
通讯作者：
Li YF