Chronic unpredictable mild stress in mice induces depressive-like behaviors and impairs sensorimotor performance, accompanied by elevated neuroinflammation. Ketamine hydrochloride, given in a sequential exposure regimen, improves sensorimotor deficits and reduces depressive-like behaviors. It also decreases microglial activation and lowers pro-inflammatory cytokine levels in the cerebrum, spinal cord, and cerebellum. The findings indicate that ketamine therapy can enhance sensorimotor function alongside its antidepressant effects, likely through modulation of central nervous system inflammation.
Prolonged treatment with ketamine did not alleviate depressive-like behavior in female mice exposed to chronic unpredictable mild stress, but it did improve anxiety-like behaviors, short-term memory, and social interaction deficits. Ketamine also increased plasma oxytocin levels and oxytocin receptor expression while reducing nitro-oxidative stress markers in intestinal and hippocampal tissues. These results suggest that although short-term ketamine has antidepressant effects, its extended use does not adequately resolve depressive-like behavior in mice.