Ketamine ameliorates postpartum depression-like behaviors in rats exposed to sevoflurane during pregnancy through the AMPK/SIRT1/NLRP3 pathway.
Journal of Affective Disorders February 14, 2026 H. Xue, Xu Yang, Shihui Kuai et al.
Repeated exposure to the general anesthetic sevoflurane during mid-gestation induces depression-like behaviors in postpartum rats. Pregnant rats exposed to 3% sevoflurane for two hours on gestational days 13-15 showed increased immobility in the forced swim test, prolonged feeding latency, reduced food consumption, and decreased movement in the open field test on postpartum day 1. These behaviors were accompanied by decreased AMPK/SIRT1 expression, activation of the NLRP3 inflammasome, microglial activation, and increased inflammatory cytokines in the hippocampus. Treatment with AICAR (an AMPK agonist), MCC950 (an NLRP3 antagonist), minocycline (a microglial activation inhibitor), or ketamine alleviated these effects, while dorsomorphin (an AMPK antagonist) reversed ketamine's antidepressant effects. The findings indicate that ketamine alleviates postpartum depression-like behaviors by reducing microglial neuroinflammation and NLRP3 inflammasome activation via the AMPK/SIRT1 signaling pathway.