The resilient phenotype elicited by ketamine against inflammatory stressors-induced depressive-like behavior is associated with NLRP3-driven signaling pathway.
Journal of Psychiatric Research September 30, 2021 A. Camargo, A. P. Dalmagro, I. A. Wolin et al.
A single injection of ketamine (5 mg/kg) given to mice one week before exposure to the inflammatory stressors lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-α) prevented depressive-like behaviors measured in the tail suspension test and splash test. A lower dose (1 mg/kg) did not have this effect. LPS increased markers of microglial activation and components of the NLRP3 inflammasome signaling pathway in the ventral hippocampus, while TNF-α only increased two of those components. Ketamine at 5 mg/kg, but not 1 mg/kg, blocked these increases. The findings suggest ketamine can promote resilience against inflammation-induced depressive-like behavior by suppressing NLRP3 inflammasome signaling.