Orexin-B antagonized respiratory depression induced by sevoflurane, propofol, and remifentanil in isolated brainstem-spinal cords of neonatal rats

Orexins (hypocretins) play a crucial role in arousal, feeding, and endocrine function. We previously reported that orexin-B activated respiratory neurons in the isolated brainstem-spinal cords of neonatal rats. We herein determined whether orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil. We recorded C4 nerve bursts as an index of inspiratory activity in a brainstem-spinal cord preparation. The preparation was superfused with a solution equilibrated with 3% sevoflurane alone for 10 min and the superfusate was then switched to a solution containing sevoflurane plus orexin-B. Sevoflurane decreased the C4 burst rate and the integrated C4 amplitude. The C4 burst rate and amplitude were reversed by 0.5 μM orexin-B, but not by 0.1 μM orexin-B. The decrease induced in the C4 burst rate by 10 μM propofol or 0.01 μM remifentanil was significantly antagonized by 0.1 μM orexin-B. Respiratory depression induced by a higher concentration (0.1 μM) of remifentanil was not restored by 0.1 μM orexin-B. These results demonstrated that orexin-B antagonized respiratory depression induced by sevoflurane, propofol, or remifentanil.