Ketamine reduces microglial activation and brain monocyte infiltration and promotes peripheral regulatory immune cells, relieving lipopolysaccharide (LPS)-induced depressive-like behavior in mice.

Ketamine has emerged as a rapid and sustained treatment for Major Depressive Disorder (MDD) and an alternative for patients who have not responded to traditional therapies. Its effects have been partly attributed to the noncompetitive antagonism of the N-methyl-D-aspartate receptor (NMDAR) in the central nervous system, which enhances neuroplasticity. However, the etiopathology of MDD is complex, and substantial evidence suggests that inflammation may significantly contribute to the initiation and maintenance of MDD. Furthermore, the rapid and sustained antidepressant effect of ketamine may be attributed to its anti-inflammatory and immunomodulatory actions. To investigate the antidepressant and anti-inflammatory effect of ketamine, we used a lipopolysaccharide (LPS)-induced depressive-like murine model. The Tail Suspension Test (TST) and Sucrose Preference Test (SPT) were conducted to assess depressive-like behaviors. Additionally, cellular immunophenotyping of blood, spleen, and brain was performed by flow cytometry. Ketamine administration (10-20 mg/kg) alleviated despair and anhedonia in LPS-depressive-like mice, as evidenced by the TST and SPT tests. Behavioral changes were accompanied by the reduction of Ly6G