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正电子发射断层扫描神经影像学显示多巴胺 D2 受体上调导致大鼠急性束缚应激模型杏仁核功能障碍。

PET neuroimaging reveals upregulation of dopamine D2 receptor contributes to amygdaloid dysfunction in rat acute restraint stress model.

机构信息

Department of Forensic Pathology, West China School of Basic Medical Sciences and Forensic Medicine, Sichuan University, Chengdu, Sichuan, 610064, China.

Department of Cardiology, Bethune Hospital Affiliated to Shanxi Medical University, Taiyuan, Shanxi, 030032, China.

出版信息

Biochem Biophys Res Commun. 2021 Jul 5;561:45-51. doi: 10.1016/j.bbrc.2021.03.135. Epub 2021 May 18.

Abstract

Acute stress relates to high prevalence of anxiety, depression or even sudden death. Although dopaminergic system in amygdala-medial prefrontal cortex (mPFC) circuit is hyper-responsive to stress-induced anxiety, the mechanisms that control anxiety still remains unanswered. Here, the acute restraint stress model(ARS) was established to develop anxiety-like behavior. The D2-dopamine receptor (D2R) availability in amygdala and mPFC was assessed using [F]-fallypride positron emission tomography(PET) and immunohistochemical assay. We revealed that ARS paradigm was successfully established, as evidenced by elevated plus-maze test(EPM) and increased corticosterone release. Moreover, PET imaging displayed elevated D2R availability in the amygdala and mPFC in ARS as compared to that in the naives. PET imaging combined with immunohistochemical assay confirmed that amygdaloid D2R was significantly implicated in stress-induced anxiety. Our findings delivered valuable insights into neuromechanism of amygdaloid D2R underlying stress-induced anxiety and might have important implications for developing therapeutics for anxiety by targeting amygdaloid D2R.

摘要

急性应激与焦虑、抑郁甚至猝死的高患病率有关。尽管杏仁核-内侧前额叶皮质(mPFC)回路中的多巴胺能系统对应激引起的焦虑反应过度,但控制焦虑的机制仍未得到解答。在这里,建立了急性束缚应激模型(ARS)以开发类似焦虑的行为。使用 [F]-fallypride 正电子发射断层扫描(PET)和免疫组织化学测定评估杏仁核和 mPFC 中的 D2-多巴胺受体(D2R)可用性。我们发现,正如高架十字迷宫测试(EPM)和皮质酮释放增加所证明的那样,ARS 范式成功建立。此外,与新手相比,PET 成像显示 ARS 中杏仁核和 mPFC 中的 D2R 可用性增加。PET 成像结合免疫组织化学测定证实,杏仁核 D2R 明显参与了应激引起的焦虑。我们的研究结果为杏仁核 D2R 介导应激诱导焦虑的神经机制提供了有价值的见解,并可能通过靶向杏仁核 D2R 为焦虑症的治疗提供重要意义。

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