Time‐Dependent Therapeutic Effect of S ‐Ketamine on PTSD Mediated by VTA‐OFC Dopaminergic Neurocircuit
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.