Department of Anesthesiology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, China.
Neurochem Res. 2021 Jun;46(6):1435-1446. doi: 10.1007/s11064-021-03284-3. Epub 2021 Mar 8.
It has been reported that systemic activation of D1 receptors promotes emergence from isoflurane-induced unconsciousness, suggesting that the central dopaminergic system is involved in the process of recovering from general anesthesia. The nucleus accumbens (NAc) contains abundant GABAergic medium spiny neurons (MSNs) expressing the D1 receptor (D1R), which plays a key role in sleep-wake behavior. However, the role of NAc D1 receptors in the process of emergence from general anesthesia has not been identified. Here, using real-time in vivo fiber photometry, we found that neuronal activity in the NAc was markedly disinhibited during recovery from propofol anesthesia. Subsequently, microinjection of a D1R selective agonist (chloro-APB hydrobromide) into the NAc notably reduced the time to emerge from propofol anesthesia with a decrease in δ-band power and an increase in β-band power evident in the cortical electroencephalogram. These effects were prevented by pretreatment with a D1R antagonist (SCH-23390). Whole-cell patch clamp recordings were performed to further explore the cellular mechanism underlying the modulation of D1 receptors on MSNs under propofol anesthesia. Our data primarily demonstrated that propofol increased the frequency and prolonged the decay time of spontaneous inhibitory postsynaptic currents (sIPSCs) and miniature IPSCs (mIPSCs) of MSNs expressing D1 receptors. A D1R agonist attenuated the effect of propofol on the frequency of sIPSCs and mIPSCs, and the effects of the agonist were eliminated by preapplication of SCH-23390. Collectively, these results indicate that modulation of the D1 receptor on the activity of NAc MSNs is vital for emergence from propofol-induced unconsciousness.
据报道，D1 受体的系统激活可促进异氟醚诱导的意识丧失，表明中枢多巴胺能系统参与了从全身麻醉中恢复的过程。伏隔核（NAc）含有丰富的表达 D1 受体（D1R）的 GABA 能中间神经元（MSNs），其在睡眠-觉醒行为中起关键作用。然而，NAc D1 受体在全身麻醉苏醒过程中的作用尚未确定。在这里，我们使用实时活体光纤光度法发现，在异丙酚麻醉恢复过程中，NAc 的神经元活动明显被去抑制。随后，将 D1R 选择性激动剂（氯-APB 氢溴化物）微注射到 NAc 中，可明显缩短异丙酚麻醉苏醒时间，同时皮质脑电图中的 δ 波段功率降低，β 波段功率增加。用 D1R 拮抗剂（SCH-23390）预处理可预防这些作用。进一步进行全细胞膜片钳记录以探讨 D1 受体在异丙酚麻醉下对 MSNs 调制的细胞机制。我们的数据主要表明，异丙酚增加了表达 D1 受体的 MSNs 的自发性抑制性突触后电流（sIPSCs）和微小 IPSC（mIPSCs）的频率并延长了其衰减时间。D1R 激动剂减弱了异丙酚对 sIPSCs 和 mIPSCs 频率的作用，并且激动剂的作用通过 SCH-23390 的预应用而消除。总之，这些结果表明，调节 NAc MSNs 上的 D1 受体对异丙酚诱导的无意识状态的苏醒至关重要。
