Post-traumatic stress disorder (PTSD) is a psychological disorder affecting many around the world. Growing evidence suggests that orexin-A is involved in the pathophysiology of depression and panic anxiety disorder. However, the role of orexin-A in PTSD remains unclear. Therefore, pharmacological manipulation of orexin-A can be a potential approach for the treatment of PTSD. Male Wistar rats were subjected to stress re-stress (SRS) by restraining them for 2 h followed by foot shock (FS) and halothane exposure on day-2 (D-2). Then the rats were weekly exposed to FS as re-stress cue . Suvorexant, an orexin antagonist (10, 20 and 30 mg/kg p.o.) and paroxetine (10 mg/kg p.o.) were administered from D-8 to D-32. Plasma and cerebrospinal fluid (CSF) were collected for corticosterone and orexin-A measurement. The analysis of serotonin and corticotropin-releasing factor receptor-1 (CRF-R1) were performed in the amygdalar tissue. SRS-induced PTSD-like symptoms like fear response, anxiety-like behaviour and hypocorticosteronism were attenuated by suvorexant and paroxetine. Interestingly, SRS exposed rats showed activation of orexin-A and serotonergic systems, which were also attenuated by suvorexant. Additionally, suvorexant ameliorated the extrahypothalamic induced upregulation of CRH-R1 in SRS-exposed rats.

Therefore, orexin-A may be considered as a neurochemical-marker for PTSD and suvorexant alleviated PTSD-like symptoms through modulating orexinergic, serotonergic and neuroendocrine systems.

创伤后应激障碍 (PTSD) 是一种影响世界各地许多人的心理障碍。越来越多的证据表明，orexin-A 参与抑郁症和恐慌性焦虑症的病理生理学。然而，orexin-A 在 PTSD 中的作用仍不清楚。因此，orexin-A 的药理学操作可以成为治疗 PTSD 的潜在方法。雄性 Wistar 大鼠通过将它们束缚 2 小时，然后在第 2 天 (D-2) 进行足部休克 (FS) 和氟烷暴露来承受压力再应激 (SRS)。然后将大鼠每周暴露于FS作为再应激提示。Suvorexant，一种食欲素拮抗剂（10、20 和 30 mg/kg po）和帕罗西汀（10 mg/kg po）从第 8 天到第 32 天给药。收集血浆和脑脊液 (CSF) 用于皮质酮和食欲素-A 测量。在杏仁核组织中进行了血清素和促肾上腺皮质激素释放因子受体-1 (CRF-R1) 的分析。suvorexant 和帕罗西汀可减轻 SRS 诱导的 PTSD 样症状，如恐惧反应、焦虑样行为和皮质酮减少症。有趣的是，SRS 暴露的大鼠显示出食欲素-A 和血清素能系统的激活，这也被 suvorexant 减弱。此外，suvorexant 改善了 SRS 暴露大鼠下丘脑外诱导的 CRH-R1 上调。

因此，orexin-A 可能被认为是 PTSD 的神经化学标志物，而 suvorexant 通过调节食欲素、血清素和神经内分泌系统减轻了 PTSD 样症状。