Xenon produces rapid antidepressant- and anxiolytic-like effects in lipopolysaccharide-induced depression mice model

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.