Role of dopamine D3 receptor in alleviating behavioural deficits in animal models of post-traumatic stress disorder
Role of dopamine D3 receptor in alleviating behavioural deficits in animal models of post-traumatic stress disorder
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多巴胺 D3 受体在缓解创伤后应激障碍动物模型行为缺陷中的作用
DOI：
10.1016/j.pnpbp.2018.03.001
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发表时间：
2018-03
影响因子：
5.6
通讯作者：
Jin Li
中科院分区：
文献类型：
--
作者：
Dake Song;Yaping Ge;Zhaodi Chen;Chao Shang;Ying Guo;Taiyun Zhao;Yunfeng Li;Ning Wu;Rui Song;Jin Li
创伤后应激障碍（PTSD）是一种复杂的精神障碍，发生在暴露于创伤事件后。PTSD的主要临床表现包括恐惧和应激失调。在动物和人类中，多巴胺功能失调似乎与条件性恐惧反应有关。先前的研究表明，多巴胺D3受体（D3 R）与精神分裂症，自闭症和物质使用障碍有关，并与情绪障碍有关。然而，很少有研究探讨D3 R在PTSD发病机制和病因中的作用。在目前的研究中，我们已经报道了D3 R基因敲除（D3 R −/−）小鼠在接受不可避免的足部电击训练后，表现出背景恐惧和抗焦虑作用的冻结时间减少。类似地，新型D3 R拮抗剂YQA 14对D3 R的高选择性阻断显著改善了大鼠PTSD单次延长应激（SPS）模型中的冻结和致焦虑样行为。此外，YQA 14选择性地减轻了WT小鼠的PTSD症状，但在D3 R −/−小鼠中没有。总之，本研究证实了阻断或敲除D3 R的抗PTSD作用，提示D3 R可能在PTSD的发病机制和病因学中起重要作用，并可能成为PTSD临床治疗的潜在靶点。
Post-traumatic stress disorder (PTSD) is a complicated psychiatric disorder, which occurs after exposure to a traumatic event. The main clinical manifestation of PTSD includes fear and stress dysregulation. In both animals and humans, dysregulation of dopamine function appears to be related to conditioned fear responses. Previous studies show that the dopamine D3 receptor (D3R) is involved in schizophrenia, autism, and substance use disorders and is related to emotional disorders. However, few studies have investigated the role of the D3R in the pathogenesis and aetiology of PTSD. In the current study, we have reported that D3R knockout (D3R−/−) mice displayed decreased freezing time of contextual fearing and anxiolytic effects following training sessions consisting of exposure to inescapable electric foot-shocks. Similarly, highly selective blockade of D3Rs by YQA14, a novel D3R antagonist, significantly ameliorated freezing and anxiogenic-like behaviours in the single-prolonged stress (SPS) model of PTSD in rats. And more, YQA14 selectively alleviated the symptoms of PTSD in WT mice but not in D3R−/−mice. In summary, this study demonstrates the anti-PTSD effects of blockade or knockout of the D3R, suggesting that the D3R might play an important role in the pathogenesis and aetiology of PTSD, and might be a potential target for the clinical management of PTSD.
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影响因子：
3.7
作者：
Glickstein, SB;DeSteno, DA;Schmauss, C
通讯作者：
Schmauss, C
DOI：
10.1007/bf03001163
发表时间：
1980-10
期刊：
The Pavlovian Journal of Biological Science : Official Journal of the Pavlovian
影响因子：
--
作者：
M. Fanselow
通讯作者：
M. Fanselow
影响因子：
4.7
作者：
Li-Ming Zhang;Nan Zhao;Wen-zhi Guo;Zeng Jin;Zhi-kun Qiu;Hong-xia Chen;Rui Xue;You-zhi Zhang;Ri-fang Yang;Yun‐feng Li
通讯作者：
Li-Ming Zhang;Nan Zhao;Wen-zhi Guo;Zeng Jin;Zhi-kun Qiu;Hong-xia Chen;Rui Xue;You-zhi Zhang;Ri-fang Yang;Yun‐feng Li
DOI：
10.1002/syn.20983
发表时间：
2012-01
期刊：
Synapse (New York, N.Y.)
影响因子：
--
作者：
Rice OV;Gardner EL;Heidbreder CA;Ashby CR Jr
通讯作者：
Ashby CR Jr
影响因子：
1.9
作者：
Nader, K;LeDoux, JE
通讯作者：
LeDoux, JE