Evaluation of Ketamine after subacute low dosage Lipopolysaccharide-activated Microglia produced depressive-like phenotype in mice

Abstract

Depression is a common mental illness, with an estimated 3.8% of global population affected. Peripheral administration of lipopolysaccharide (LPS) culminate in a distinct depressive-like behavioral syndrome, measured by increased duration of immobility in the forced swim test (FST) and anhedonia in sucrose preference tests (SPT). After 6 days of LPS stimulation, we established a depression model in C57BL/6 mice, where animals started to recover from the B/W loss brought on by the LPS and the significant immunological response that resulted in microglial activation in the brain. There was a modulation in the relative weight of the thymus and spleen observed under these experimental conditions. Ketamine having a quick onset of action reduces the emergence of depressive-like behaviour by modifying the intensity of Iba-1 in stressed mice by reducing swimming behaviour and boosting desire for sucrose. However, it did not result in an improvement in the number of microglia or CD11b cells activation in the hippocampus of C57BL/6 mice or in the relative weights of the spleen and thymus. In summary, these data emphasizes that Ketamine treatment improves depressive-like behavior and Iba-1 immunoreactivity, but the hyperactive in terms of number of microglia and CD11b expression were not modulated in the mouse hippocampus.