Sevoflurane induces neuronal activation and behavioral hyperactivity in young mice

Sevoflurane, a commonly used anesthetic, may cause agitation in patients. However, the mechanism underlying this clinical observation remains largely unknown. We thus assessed the effects of sevoflurane on neuronal activation and behaviors in mice. Ten-day-old mice received 2% sevoflurane, 1% isoflurane, or 6% desflurane for 10 minutes. The behavioral activities were recorded and evaluated at one minute after the loss of righting reflex in the mice, which was about two minutes after the anesthetic administration. The neuronal activation was evaluated by c-Fos expression and calcium imaging at one minute after the anesthetic administration. Propofol, which reduces neuronal activation, was used to determine the cause-and-effect of sevoflurane. We found that sevoflurane caused an increase in neuronal activation in primary somatosensory cortex of young mice and behavioral hyperactivity in the mice at one minute after the loss of righting reflex. Desflurane did not induce behavioral hyperactivity and isoflurane only caused behavioral hyperactivity with borderline significance. Finally, propofol attenuated the sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These results demonstrate an unexpected sevoflurane-induced increase in neuronal activation and behavioral hyperactivity in young mice. These findings suggest the potential mechanisms underlying the sevoflurane-induced agitation and will promote future studies to further determine whether anesthetics can induce behavioral hyperactivity via increasing neuronal activation.