Circadian differences in emergence from volatile anaesthesia in mice: involvement of the locus coeruleus noradrenergic system.

Abstract

Circadian differences in the induction, maintenance, or emergence from volatile anaesthesia have not been well studied. The minimal alveolar concentration (MAC) for preventing movement in response to a painful stimulus, MAC for loss of righting reflex (MAC_LORR), and MAC for recovery of righting reflex (MAC_RORR) in C57BL/6J male mice with isoflurane or sevoflurane exposure were measured during either the light or dark phase. Time to onset of loss of righting reflex (Time_LORR) and recovery of righting reflex (Time_RORR) upon exposure to 1 MAC of isoflurane or sevoflurane were determined. EEG was also monitored in the light and dark phase under isoflurane or sevoflurane exposure. The noradrenergic toxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) was used to deplete noradrenergic neurones in the locus coeruleus to explore the impact of norepinephrine on these measurements. MAC_LORR, Time_LORR, and MAC did not show light- or dark-phase-dependent variations for either isoflurane or sevoflurane exposure. However, MAC_RORR was higher and Time_RORR was shorter in the dark phase than in the light phase for both isoflurane and sevoflurane exposure. The EEG delta wave power was higher but theta wave power was lower in the light phase than that in the dark phase during the rest state and emergence of anaesthesia. These light- and dark-phase-dependent changes in emergence were abolished in DSP-4-treated mice. Our data show that circadian differences exist during emergence but not during induction or maintenance of sevoflurane or isoflurane anaesthesia. The locus coeruleus noradrenergic system may contribute to these differences.