Antidepressant-like effects of ketamine involve CX3CL1/CX3CR1 signaling-mediated synaptic plasticity in the mPFC
Translational Psychiatry July 20, 2026 Yong-Yu Yin, Si-Rui Sun, Hui-Ying Zhang et al.
Ketamine, a fast-acting antidepressant, works in part by blocking a signaling pathway between immune cells and neurons in the brain. In mice with depression-like symptoms caused by corticosterone, a single dose of ketamine (10 mg/kg) reversed behavioral deficits, reduced inflammation, and restored the structure of brain cells. Blocking the CX3CL1/CX3CR1 signaling pathway—either with a drug or by silencing the gene—eliminated both the behavioral and brain-cell benefits of ketamine. This suggests that this chemokine pathway is essential for ketamine's antidepressant effects and could be a new target for treating depression.