Ketamine abrogates sensorimotor deficits and cytokine dysregulation in a chronic unpredictable mild stress model of depression.
Edem Ekpenyong Edem, Collins-kevin Chukwudi Anyanwu, Kate Eberechukwu Nebo, Elizabeth Toyin Akinluyi, Adedamola Adediran Fafure, Azeez Olakunle Ishola, Linus Anderson Enye
Psychopharmacology January 1, 2022 Peer reviewed DOI: 10.1007/s00213-021-06021-4 via PubMed
Summary
Ketamine hydrochloride can improve sensorimotor performance and reduce inflammation in a mouse model of major depressive disorder (MDD) induced by chronic unpredictable mild stress (CUMS). The study demonstrated that ketamine therapy led to significant improvements in sensorimotor deficits and decreased levels of pro-inflammatory cytokines and microglial activation in the brain regions assessed. These findings suggest a link between the therapeutic effects of ketamine and its ability to modulate inflammation associated with MDD.
Study at a glance
| Population | mouse model of major depressive disorder |
|---|---|
| Key finding | Ketamine therapy improved sensorimotor deficits and reduced inflammation in a mouse model of major depressive disorder. |
Abstract
Major depressive disorder (MDD) is a serious mental disorder with influence across the functional systems of the body. The pathogenesis of MDD has been known to involve the alteration of normal body functions responsible for the normal inflammation processes within the CNS; this along with other effects results in the depreciation of the sensorimotor performance of the body. Ketamine hydrochloride, a novel antidepressant agent, has been used as a therapeutic agent to treat MDD with its efficacy stretching as far as enhancing sensorimotor performance and restoring normal cytokine levels of the CNS. While these therapeutic actions of ketamine may or may not be related, this study made use of chronic unpredictable mild stress (CUMS) to generate the mouse model of depression. The efficacy of ketamine as an antidepressant following sequential exposure and co-administrative treatment protocols of administration was evaluated using behavioural tests for sensorimotor performance and depressive-like behaviours. Its effect in managing CNS inflammation was assessed via the biochemical analysis of inflammatory cytokine levels in the cerebrum, spinal cord and cerebellum; and immunohistochemical demonstration of microglial activity in the corpus striatum and cerebellum. The sensorimotor performance which had been diminished by CUMS showed greater improvement under the sequential exposure regimen of ketamine. Ketamine was also efficacious in decreasing the level of inflammation with an evident reduction in microglial activation and pro-inflammatory cytokines in the studied regions, following CUMS exposure. Taken together, our study indicates that ketamine therapy can improve sensorimotor deficits co-morbid with a depressive disorder in parallel with modulation of the inflammatory system.