Major depressive disorder (MDD) is a leading cause of disability worldwide, and current antidepressants are limited by delayed onset and incomplete efficacy. Esketamine produces antidepressant effects more rapidly than conventional treatments, but its underlying mechanisms remain unclear. We examined whether cannabinoid type 1 receptor (CB1R) signaling is associated with hippocampal...
Advanced ScienceSeptember 25, 2025Ye Wang, Lei Liu, Jinghao Wang et al.2 citations
Current pharmacotherapies for post-traumatic stress disorder (PTSD) are limited by delayed onset and side effects. Despite ketamine exhibiting rapid relief of the core symptoms of PTSD, its clinical efficacy varies considerably depending on the timing of drug delivery. However, the underlying mechanism remains unclear. In this study, the therapeutic effects of early (day 1) and late (day 7)...
The mechanisms underlying esketamine's therapeutic effects remain elusive. The study aimed to explore the impact of single esketamine treatment on LPS-induced adolescent depressive-like behaviors and the role of Nrf2 regulated neuroinflammatory response in esketamine-produced rapid antidepressant efficacy. Adolescent male C57BL/6J mice were randomly assigned to three groups: control, LPS, and...
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...
Repeated, long-term (weeks to months) exposure to standard antidepressant medications is required to achieve treatment efficacy. In contrast, acute ketamine quickly improves mood for an extended time. Recent work implicates that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are involved in mediating ketamine's antidepressant effects. In this study, we directly targeted HCN...
Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear. Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex...
Numerous antidepressants are available for the treatment of the major depressive disorder (MDD). Unfortunately, the disadvantages of these antidepressive medications, including inadequate treatment response, the therapeutic lag between drug administration and the onset of symptoms alleviation, and the safety consideration limit their clinical use and accelerate the exploration of advanced...