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 2022 DOI: 10.1007/s00213-021-06021-4 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study using a mouse model Peer reviewed |
|---|---|
| Population | Mice exposed to chronic unpredictable mild stress |
| Intervention | Ketamine hydrochloride |
| Topics | Depression Esketamine Ketamine |
| Keywords | Cytokines Ketamine hydrochloride Neuroinflammation Sensorimotor performance |
| Citations | 9 |
| Key findings | Ketamine therapy improves sensorimotor deficits co-morbid with depressive disorder in parallel with modulation of the inflammatory system. |
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.
Comparable studies
Other preclinical and animal studies on ketamine for depression, most cited first.
Citations in the library
Cited by 4
- Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile Drug Discovery Today February 1, 2023
- Mechanism of antidepressant action of ketamine and differences between its two enantiomers. Journal of Anesthesia and Translational Medicine September 1, 2025
- Temporal Immune Effects of Oral Ketamine on PTSD: Transcriptomic Evidence of Short-Term Inflammation Suppression and Long-Term Immune Remodelling medRxiv Preprint Server May 26, 2025
- Novel and emerging anesthetic drugs for the treatments of major depression: a comprehensive review of efficacy, mechanism, and outlook. Frontiers in Psychiatry 2025
Cites 9
- Ketamine: a paradigm shift for depression research and treatment Neuron March 1, 2019
- Ketamine – More mechanisms of action than just NMDA blockade Trends in Anaesthesia and Critical Care March 22, 2014
- Ketamine and depression: a narrative review Drug Design, Development and Therapy August 1, 2019
- Stress-sensitive antidepressant-like effects of ketamine in the mouse forced swim test PLoS One April 15, 2019
- Effects of ketamine on the unconditioned and conditioned locomotor activity of preadolescent and adolescent rats: impact of age, sex, and drug dose. Psychopharmacology September 2017
and 4 more in the library