A Sleep-Specific Midbrain Target for Sevoflurane Anesthesia

Sevoflurane has been the most widely used inhaled anesthetics with a favorable recovery profile; however, the precise mechanisms underlying its anesthetic action are still not completely understood. Here the authors show that sevoflurane activates a cluster of urocortin 1 (UCN1(+))/cocaine- and amphetamine-regulated transcript (CART(+)) neurons in the midbrain involved in its anesthesia. Furthermore, growth hormone secretagogue receptor (GHSR) is highly enriched in sevoflurane-activated UCN1(+)/CART(+) cells and is necessary for sleep induction. Blockade of GHSR abolishes the excitatory effect of sevoflurane on UCN1(+)/CART(+) neurons and attenuates its anesthetic effect. Collectively, their data suggest that anesthetic action of sevoflurane necessitates the GHSR activation in midbrain UCN1(+)/CART(+) neurons, which provides a novel target including the nucleus and receptor in the field of anesthesia.

Automated summary

The authors demonstrate that sevoflurane activates a specific group of neurons in the midbrain, promoting sleep induction and offering anesthetic effects. These neurons express high levels of GHSR, and blocking GHSR diminishes the excitatory effect of sevoflurane and attenuates its anesthetic effect. This study provides a novel target in the field of anesthesia involving the activation of GHSR in midbrain neurons.