Combined Exposure to Chronic Sleep Deprivation and Caffeine Potentiates Behavioural Deficits by Altering Neurochemical Profile and Synaptophysin Expression in Long-Evans Rats

Abstract

Using the Unpredictable Chronic Sleep Deprivation (UCSD) paradigm we developed, the combined effects of chronic sleep deprivation and high caffeine intake on prefrontal cortical synaptophysin expression, neurochemical profiles, and behavioural outcomes in Long-Evans rats were evaluated. The combination of chronic sleep deprivation and high-dose caffeine treatment produced varying degrees of behavioural impairments, depletion of antioxidants, serotonin, and an upregulation of acetylcholinesterase (AChE) activity in the prefrontal cortex. An immunohistochemical assessment revealed a reduction in synaptophysin protein expression in the prefrontal cortex following exposure to high-dose caffeine and chronic sleep deprivation. Overall, our findings support the advocacy for adequate sleep for optimal mental performance as a high intake of caffeine to attenuate the effects of sleep deprivation that may alter the neurochemical profile and synaptic plasticity in the prefrontal cortex, significantly increasing the risk of neuropsychiatric/degenerative disorders.

Keywords: Caffeine; Cholinergic system; Oxidative stress; Prefrontal cortical synaptic plasticity; Serotonergic system; Unpredictable Chronic Sleep Deprivation.