Effects of orexin-A on propofol anesthesia in rats

Abstract

An active sleep homeostatic process is present during propofol anesthesia. Activation of the orexin system induces wakefulness, and inhibition of the orexin system causes narcolepsy. We hypothesized that orexin would affect propofol anesthesia. The effects of an intracerebroventricular (i.c.v.) injection of orexin-A (OXA) or an orexin-1 (OX-1) receptor antagonist, SB-334867, on the times to the loss and return of the righting reflex induced by propofol were examined in Wistar rats. The effects of propofol or OXA on norepinephrine (NE) and dopamine (DA) release from the prefrontal cortex (PFC) were examined using in vivo microdialysis. An i.c.v. injection of OXA (1nmol) decreased the time to emergence from propofol anesthesia mediated by the OX-1 receptor without changing anesthetic induction (n=8). An i.c.v. injection of SB-334867 (5 and 50nmol) increased the time to emergence from propofol anesthesia without changing anesthetic induction (n=8). Intravenous infusion of propofol decreased NE (48±8%; n=8) and DA (61.2±11%; n=8) release from PFC mediated by the GABA(A) receptor. An i.c.v. injection of OXA reversed the decreases in NE and DA release induced by propofol mediated by the OX-1 receptor (n=8). These results indicate that the orexin system may accelerate the emergence from propofol anesthesia associated with increases in the central noradrenergic and dopaminergic activity.