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.

Individually, sleep deprivation and sub-chronic tramadol exposure have been reported to impair visual processes, however the underlying mechanisms of their combined effects are largely unknown. Thus, this study investigated the role of tramadol hydrochloride on lipid-immune activities in the ocular tissue and visual cortex of sleep-deprived periadolescent rats. Sixty female periadolescent Wistar rats were either sleep-deprived with or without tramadol treatment. Following euthanasia, brain and whole eye tissues were collected for biochemical and immunohistochemical assays. Results revealed impaired ocular tissue lipid profile following sleep deprivation (SD). Sleep deprivation also induced lipid peroxidation; upregulated apolipoprotein E (ApoE), and nuclear factor kappa B (NF-κB) 1 levels in the ocular tissue. Furthermore, chronic SD exposure triggered gliosis with marked increase in astrocyte and microglia counts in the visual cortex. However, treatment with tramadol restored ocular tissue lipid function markers, downregulated ocular tissue NF-κB levels, as well as ameliorated sleep deprivation-induced gliosis in the visual cortex. Taken together, this study demonstrates the role of tramadol in improving inflammatory processes and lipid homeostasis in the visual system by modulating ocular tissue ApoE and NF-κB signalling, and attenuating gliosis in the visual cortex of sleep-deprived rats.