Esketamine ameliorates depression-like behavior in mice via modulation of the NRG1-ErbB4 pathway.
Frontiers in psychiatry January 1, 2026 Hang Yu, Yuqiong Zhu, Jie Wang et al.
In a mouse model of depression induced by chronic social defeat stress, susceptible mice showed reduced social interaction, lower sucrose preference, decreased NRG1 protein expression in the prefrontal cortex, and increased immobility time compared to controls. A subanesthetic dose of esketamine increased NRG1 expression in the prefrontal cortex within 30 minutes and improved social interaction and reduced immobility at both 30 minutes and 24 hours post-injection. No significant changes were observed in GAD67 or ErbB4 expression. Esketamine may rapidly improve depressive-like behavior by regulating the NRG1-ErbB4 signaling pathway.