Neuroscience
February 16, 2025
Xinxu Ma, Shanshan Xue, Hongzhe Ma et al.
12 citations
A single dose of esketamine alleviates depressive-like behaviors in adolescent male mice exposed to the inflammatory agent LPS. The antidepressant effect is linked to increased expression of the Nrf2 protein and reduced levels of inflammatory cytokines (TNF-α, IL-1β, iNOS) in the brain's prefrontal cortex and hippocampus. Blocking Nrf2 with the inhibitor ML385 reversed both the behavioral and anti-inflammatory effects of esketamine. In the blood, esketamine also reduced pro-inflammatory and increased anti-inflammatory cytokines, an effect again blocked by Nrf2 inhibition. The findings suggest esketamine's rapid antidepressant action may work through activating Nrf2-mediated anti-inflammatory signaling.
Frontiers in psychiatry
January 1, 2024
Haixia Chen, Xinxin Zhao, Xinxu Ma et al.
9 citations
A single dose of esketamine rapidly alleviated depressive- and anxiety-like behaviors in mice exposed to chronic variable stress, an effect comparable to seven days of repeated fluoxetine treatment. The stress protocol increased plasma levels of multiple inflammatory cytokines (IL-1β, IL-6, IL-8, IL-17A, TNFα, IL-4, IL-9, IL-24, IL-37, IFN-β, and CXCL12) and decreased IL-10 and IL-33. Both esketamine and fluoxetine partially normalized these inflammatory disturbances. The findings suggest that esketamine's rapid antidepressant action may involve normalizing inflammatory cytokine expression.
Depressive Disorders: Mechanisms, Measurement and Management
January 1, 2019
Min Cai, Huaning Wang, Xia Zhang
4 citations
Many antidepressants exist for major depressive disorder, but their limitations—poor response, delayed onset, and safety concerns—drive the search for new drugs with novel mechanisms and fewer side effects. This chapter reviews compounds showing clinical promise in various phase trials. Though most strategies currently address treatment-resistant depression, some, like ketamine, may become routine. The review covers mechanisms involving glutamatergic, opiate, and cholinergic receptors, as well as neuroplasticity, and includes supplemental approaches such as polyunsaturated fatty acids for their antidepressant properties.
Advanced Science
September 25, 2025
Ye Wang, Lei Liu, Jinghao Wang et al.
2 citations
Early administration of S-Ketamine (on day 1) after trauma significantly improves PTSD symptoms in rodent models, particularly impaired fear extinction, while late administration (day 7) does not. The firing and burst rates of dopamine neurons in the ventral tegmental area (VTA) decrease after PTSD modeling and are restored only by early S-Ketamine. These VTA dopamine neurons respond to conditioned stimuli and help replace aversive memory encoding during fear extinction. Inhibiting the VTA-to-orbitofrontal cortex (OFC) pathway blocks S-Ketamine's therapeutic effect. A non-invasive brain stimulation targeting the OFC sensitizes cortical dopaminergic transmission and extends the effective time window of S-Ketamine for anti-PTSD treatment.