Department of Senile Disease, The Third Hospital of Hebei Medical University.
Neuroscience Research Center, Institute of Medical and Health Science of HeBMU.
Neuroreport. 2020 Mar 25;31(5):387-393. doi: 10.1097/WNR.0000000000001415.
Onset delay of current antidepressants is always the most significant limitation for the treatment of depression. More attention has been given to the glutamate acid system for developing fast-onset antidepressants. Xenon, acting as a well-known N-methyl-D-aspartate receptors antagonist, has been widely used clinically as anesthetics and was reported to exert antidepressant-like effects in rats under normal condition. The robust and rapid-acting antidepressant- and anxiolytic-like activities of xenon through the use of depression rodent model are still elusive. By using lipopolysaccharide-induced depression mice models, the present study aimed to evaluate the fast-acting antidepressant-like effects of xenon pretreatment. Behavioral tests, mainly including open-field test, novelty-suppressed feeding test, sucrose preference test, tail suspension test, and forced swimming test, were conducted respectively. Our results showed that both xenon gas and xenon-rich saline pretreatment intraperitoneally produced significant antidepressant- and anxiolytic-like activities in mice under normal condition. Further, xenon gas pretreatment (intraperitoneally) rapidly blocked lipopolysaccharide-induced depression- and anxiety-like behaviors of mice. These findings provide direct evidence that xenon could produce fast-onset antidepressant- and anxiolytic-like activities, which highlights the possibility to develop xenon as a promising fast-acting drug for treatment of depression, anxiety, and even other stress-related diseases.
目前，抗抑郁药物的起效时间一直是治疗抑郁症的最大限制。因此，人们越来越关注谷氨酸酸系统，以开发快速起效的抗抑郁药物。氙气作为一种众所周知的 N-甲基-D-天冬氨酸受体拮抗剂，已广泛应用于临床麻醉，并被报道在正常情况下对大鼠具有抗抑郁样作用。然而，氙气通过使用抑郁啮齿动物模型来产生强大且快速起效的抗抑郁和抗焦虑样作用的机制仍难以捉摸。本研究通过使用脂多糖诱导的抑郁小鼠模型，旨在评估氙气预处理的快速起效的抗抑郁样作用。主要包括旷场试验、新奇抑制性摄食试验、蔗糖偏好试验、悬尾试验和强迫游泳试验等行为学测试。结果表明，氙气和富含氙气的生理盐水预处理均可显著改善正常状态下小鼠的抗抑郁和抗焦虑样行为。此外，氙气预处理（腹腔内）可迅速阻断脂多糖诱导的小鼠抑郁和焦虑样行为。这些发现为氙气能够产生快速起效的抗抑郁和抗焦虑样作用提供了直接证据，这凸显了开发氙气作为治疗抑郁症、焦虑症甚至其他应激相关疾病的有前途的快速作用药物的可能性。
