Effects of esketamine and fluoxetine on depression-like behaviors in chronic variable stress: a role of plasma inflammatory factors.
Haixia Chen, Xinxin Zhao, Xinxu Ma, Hongzhe Ma, Cuihong Zhou, Yunyun Zhang, Zhengwu Peng, Shanshan Xue, Min Cai
Frontiers in Psychiatry 2024 DOI: 10.3389/fpsyt.2024.1388946 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Mice exposed to chronic variable stress |
| Interventions | Esketamine Fluoxetine |
| Dose | single dose or 7-day repeated administration |
| Duration | 21-day chronic variable stress protocol followed by single dose or 7-day repeated administration |
| Topics | Depression Esketamine |
| Keywords | Chronic variable stress Fluoxetine Inflammatory cytokines Depression treatment Antidepressant medication Psychiatric research Inflammation biomarkers Mental health |
| Citations | 9 |
| Key findings | A single dose of esketamine rapidly reversed depressive- and anxiety-like behaviors and partially normalized stress-induced changes in plasma inflammatory cytokines in mice, similar to repeated fluoxetine treatment. |
Abstract
Mounting evidence has identified the rapid and sustained antidepressive and anxiolytic-like effects of esketamine. However, the underlying mechanism of this no-monoamine target rapid-onset antidepressant is still underexplored. Immune-inflammatory pathways and cell-mediated immune activation, mainly including inflammatory cytokines in plasma, play a pivotal role in the pathogenesis of major depressive disorder and are also a potential therapeutic target for MDD. The current study was designed to clarify the role of esketamine on the expression of plasma cytokines in a depressive-like model introduced by chronic variable stress (CVS). In this study, a 21-day consecutive CVS protocol was applied to produce depressive- and anxiety-like behaviors. After the single dose or 7-day repeated administration of esketamine or fluoxetine, the depressive- and anxiety-like behaviors and the expression of inflammatory cytokines in plasma were examined. Both a single dose of esketamine and 7-days repeated fluoxetine administration elicited anti-depressive and anxiolytic effects in mice exposed to CVS. Additionally, CVS produced significant changes in the plasma inflammatory factors, notably increasing the expression of IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12, while reducing IL-10 and IL-33. With the administration of esketamine and fluoxetine, CVS-produced inflammatory disturbances were partially normalized. Together, our findings provide a novel insight that acute esketamine treatment could rescue CVS-produced depressive-like and anxiety-like behaviors in mice by normalizing the expression of inflammatory cytokines; this effect was similar to the repeated administration of fluoxetine. These results contributed to the understating of rapid anti-depressant effects elicited by esketamine.
Comparable studies
Other preclinical and animal studies on esketamine for depression, most cited first.