Withdrawal Notice: The Role of the Central Histaminergic System in Emergence from Propofol Anesthesia

Abstract

Background: The mechanisms of emergence from general anesthesia remain to be elucidated. Recent studies indicate that the central histaminergic system plays a critical role in maintaining wakefulness. Methods: Role of the central histaminergic system in emergence from propofol anesthesia using microinjections and single-unit recordings in rats was evaluated. Results: Intracerebroventricular (icv) microinjections of histamine decreased the emergence time in a dose-dependent manner and had an excitatory effect on the firing activity of medial prefrontal cortex (mPFC) neurons, while the decrease of emergence time was completely reversed by the pre-treatment with triprolidine (80 μg/5 μl) but not cimetidine (100 μg/5 μl). Moreover, the presumed histaminergic neurons fired in a state-dependent manner, and there was a dramatic increase in firing activity before regain of righting reflex. Furthermore, bidirectional manipulations of emergence were achieved through the microinjection of GABA (10 μg/side) and a potent H3 receptor inverse agonist ciproxian (1 μg/side) into the posterior hypothalamus, where the tuberomammillary nucleus (TMN) resides. Conclusion: Combining the behavioral and neurophysiologic evidence, the central histaminergic system promotes emergence from propofol anesthesia in rats. Our findings suggest an important role of the central histaminergic system in a broader field of state transitions, such as emergence from propofol anesthesia.