Department of Biology, College of Humanities & Sciences, Virginia Commonwealth University, Richmond, VA 23298, USA.
Departments of Neurology, School of Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA.
Int J Environ Res Public Health. 2020 Jun 30;17(13):4710. doi: 10.3390/ijerph17134710.
Approximately 33% of U.S. soldiers from the first Gulf War suffer from a multi-system disorder known as the Gulf War Illness (GWI). GW veterans suffer from a cluster of symptoms that prominently include fatigue and can include mood-related symptoms Compared to traditional antidepressants, ketamine (KET) produces a fast-onset and long-lasting antidepressant response, but assessments of KET for GWI-related depression are lacking. The etiology of GWI is multi-factorial and exposure to organophosphates (OP) during deployment is one of the factors underlying GWI development. Here, male Sprague-Dawley rats were repeatedly exposed to an OP DFP and three months later these rats, when assessed on a battery of rodent behavioral assays, displayed signs consistent with aspects of GWI characteristics. When treated with a sub-anesthetic dose of KET (3, 5, or 10 mg/kg, i.p.), DFP-treated rats exhibited a significant improvement in immobility time, open-arm exploration, and sucrose consumption as early as 1 h and much of these effects persisted at 24-h post-KET injection. KET's stereoisomers, -KET and -KET, also exhibited such effects in DFP rats, with -KET being the more potent isomer. Our studies provide a starting point for further assessment of KET for GWI depression.
约 33%的第一次海湾战争美国士兵患有多种系统紊乱疾病，称为海湾战争病（GWI）。海湾战争老兵患有一系列症状，主要包括疲劳，并且可能包括与情绪相关的症状。与传统的抗抑郁药相比，氯胺酮（KET）产生快速起效和持久的抗抑郁反应，但缺乏对 KET 治疗 GWI 相关抑郁症的评估。GWI 的病因是多因素的，部署期间接触有机磷酸酯（OP）是 GWI 发展的因素之一。在这里，雄性 Sprague-Dawley 大鼠反复暴露于 OP DFP 中，三个月后，这些大鼠在一系列啮齿动物行为测定中表现出与 GWI 特征某些方面一致的迹象。当用亚麻醉剂量的 KET（3、5 或 10mg/kg，ip）治疗时，DFP 处理的大鼠在 1 小时内表现出明显的不动时间、开放臂探索和蔗糖消耗的改善，并且许多这些作用在 KET 注射后 24 小时仍持续存在。KET 的立体异构体，-KET 和 -KET，在 DFP 大鼠中也表现出这种作用，其中 -KET 是更有效的异构体。我们的研究为进一步评估 KET 治疗 GWI 抑郁症提供了起点。
