Effects of propofol and sevoflurane on social and anxiety-related behaviours in sleep-deprived rats

Br J Anaesth. 2023 Sep;131(3):531-541. doi: 10.1016/j.bja.2023.05.025. Epub 2023 Aug 4.

Abstract

Background: Sleep disorders can profoundly affect neurological function. We investigated changes in social and anxiety-related brain functional connectivity induced by sleep deprivation, and the potential therapeutic effects of the general anaesthetics propofol and sevoflurane in rats.

Methods: Twelve-week-old male Sprague-Dawley rats were subjected to sleep deprivation for 20 h per day (from 14:00 to 10:00 the next day) for 4 consecutive weeks. They were free from sleep deprivation for the remaining 4 h during which they received propofol (40 mg kg-1 i.p.) or sevoflurane (2% for 2 h) per day or no treatment. These cohorts were instrumented for EEG/EMG recordings on days 2, 14, and 28. Different cohorts were used for open field and three-chambered social behavioural tests, functional MRI, nuclear magnetic resonance spectroscopy, and positron emission tomography imaging 48 h after 4 weeks of sleep deprivation.

Results: Propofol protected against sleep deprivation-induced anxiety behaviours with more time (44.7 [8.9] s vs 24.2 [4.1] s for the sleep-deprivation controls; P<0.001) spent in the central area of the open field test and improved social preference index by 30% (all P<0.01). Compared with the sleep-deprived rats, propofol treatment enhanced overall functional connectivity by 74% (P<0.05) and overall glucose metabolism by 30% (P<0.01), and improved glutamate kinetics by 20% (P<0.05). In contrast, these effects were not found after sevoflurane treatment.

Conclusions: Unlike sevoflurane, propofol reduced sleep deprivation-induced social and anxiety-related behaviours. Propofol might be superior to sevoflurane for patients with sleep disorders who receive anaesthesia, which should be studied in clinical studies.

Keywords: REM sleep; functional connectivity; propofol; sevoflurane; sleep deprivation; social behaviour.

MeSH terms

  • Anesthetics, Inhalation* / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Anxiety*
  • Male
  • Methyl Ethers* / pharmacology
  • Propofol* / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane / pharmacology
  • Sleep
  • Sleep Deprivation*
  • Social Behavior

Substances

  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Methyl Ethers
  • Propofol
  • Sevoflurane