OBJECTIVES: To assess the regulatory effect of cannabidiol (CBD) on circadian rhythm sleep disorders following general anesthesia and explore its potential mechanism in a rat model of propofol-induced rhythm sleep disorder.
METHODS: An electrode was embedded in the skull for cortical EEG recording in 24 male SD rats, which were randomized into control, propofol, CBD treatment, and diazepam treatment groups (=6). Eight days later, a single dose of propofol (10 mg/kg) was injected via the tail vein with anesthesia maintenance for 3 h in the latter 3 groups, and daily treatment with saline, CBD or diazepam was administered via gavage; the control rats received only saline injection. A wireless system was used for collecting EEG, EMG, and body temperature data within 72 h after propofol injection. After data collection, blood samples and hypothalamic tissue samples were collected for determining serum levels of oxidative stress markers and hypothalamic expressions of the key clock proteins. n
RESULTS: Compared with the control rats, the rats with CBD treatment showed significantly increased sleep time at night (20:00-6:00), especially during the time period of 4:00-6:00 am. Compared with the rats in propofol group, which had prolonged SWS time and increased sleep episodes during 18:00-24:00 and sleep-wake transitions, the CBD-treated rats exhibited a significant reduction of SWS time and fewer SWS-to-active-awake transitions with increased SWS aspects and sleep-wake transitions at night (24:00-08:00). Diazepam treatment produced similar effect to CBD but with a weaker effect on sleep-wake transitions. Propofol caused significant changes in protein expressions and redox state, which were effectively reversed by CBD treatment.
CONCLUSIONS: CBD can improve sleep structure and circadian rhythm in rats with propofol-induced sleep disorder possibly by regulating hypothalamic expressions of the key circadian clock proteins, suggesting a new treatment option for perioperative sleep disorders.
