Department of Anesthesiology, The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310006, China.
Medical College of Jining Medical University, Ningji, 272067, Shandong, China.
Mol Neurobiol. 2023 Dec;60(12):6931-6948. doi: 10.1007/s12035-023-03519-0. Epub 2023 Jul 29.
General anesthesia is widely used in various clinical practices due to its ability to cause loss of consciousness. However, the exact mechanism of anesthesia-induced unconsciousness remains unclear. It is generally thought that arousal-related brain nuclei are involved. 5-Hydroxytryptamine (5-HT) is closely associated with sleep arousal. Here, we explore the role of the 5-HT system in anesthetic awakening through pharmacological interventions and optogenetic techniques. Our data showed that exogenous administration of 5-hydroxytryptophan (5-HTP) and optogenetic activation of 5-HT neurons in the dorsal raphe nucleus (DR) could significantly shorten the emergence time of sevoflurane anesthesia in mice, suggesting that regulation of the 5-HT system using both endogenous and exogenous approaches could mediate delayed emergence. In addition, we first discovered that the different 5-HT receptors located in the DR, known as 5-HT autoreceptors, are essential for the regulation of general anesthetic awakening, with 5-HT1A and 5-HT2A/C receptors playing a regulatory role. These results can provide a reliable theoretical basis as well as potential targets for clinical intervention to prevent delayed emergence and some postoperative risks.
全身麻醉因其能引起意识丧失而被广泛应用于各种临床实践中。然而，麻醉诱导意识丧失的确切机制尚不清楚。人们普遍认为涉及到与觉醒相关的脑核。5-羟色胺（5-HT）与睡眠觉醒密切相关。在这里，我们通过药理学干预和光遗传学技术来探索 5-HT 系统在麻醉苏醒中的作用。我们的数据表明，外源性给予 5-羟色氨酸（5-HTP）和光遗传学激活中缝背核（DR）的 5-HT 神经元可以显著缩短七氟醚麻醉的苏醒时间，这表明通过内源性和外源性途径调节 5-HT 系统可以介导苏醒延迟。此外，我们首次发现位于 DR 的不同 5-HT 受体（称为 5-HT 自身受体）对于调节全身麻醉苏醒至关重要，其中 5-HT1A 和 5-HT2A/C 受体发挥调节作用。这些结果可以为临床干预提供可靠的理论依据和潜在的靶点，以预防苏醒延迟和一些术后风险。
