Involvement of Ventral Periaqueductal Gray Dopaminergic Neurons in Propofol Anesthesia
Involvement of Ventral Periaqueductal Gray Dopaminergic Neurons in Propofol Anesthesia
复制标题
腹侧导水管周围灰色多巴胺能神经元在异丙酚麻醉中的参与
DOI：
10.1007/s11064-018-2486-y
复制
发表时间：
2018-04-01
影响因子：
4.4
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Li, Jia;Yu, Tian;Zhang, Yi
据报道，中枢多巴胺能系统参与全身麻醉的潜在机制。中脑腹侧导水管周围灰质（vPAG）中的多巴胺（DA）神经元是否参与全身麻醉以及全身麻醉药如何影响这些神经元，相关文献记载仍然很少。为了确定vPAG DA神经元在丙泊酚诱导的麻醉中的作用，我们将6 - 羟基多巴胺（6 - OHDA）微量注射到vPAG以损伤DA神经元，并研究体感脑电图（EEG）的变化以及丙泊酚麻醉的诱导时间和恢复时间。随后，我们使用全细胞膜片钳技术检测丙泊酚对vPAG中DA神经元电生理活动的影响。6 - OHDA微量注射两周后，与溶媒对照组大鼠相比，6 - OHDA处理组大鼠vPAG中的DA神经元显著减少了63.6%。这种损伤显著缩短了丙泊酚麻醉的诱导时间（7.15±3.97秒对11.18±2.83秒，P < 0.05），并延长了恢复时间（780.26±150.86秒对590.68±107.97秒，P < 0.05）。同时，体感皮层脑电图显示，6 - OHDA处理组大鼠的δ波功率（0 - 4Hz）显著高于溶媒对照组大鼠。在电生理实验中，丙泊酚降低了自发性兴奋性突触后电流的频率，但不影响其幅度和衰减时间。此外，丙泊酚优先增加了自发性抑制性突触后电流的频率并延长了其衰减时间，但不影响其幅度。意义：丙泊酚可促进突触前γ - 氨基丁酸（GABA）释放，抑制突触前谷氨酸释放，并增加突触后GABA（A）受体敏感性，最终抑制vPAG DA神经元的活动，从而影响意识状态。
It has been reported that central dopaminergic system is implicated in the mechanism underlying general anesthesia. Whether dopamine (DA) neurons in midbrain ventral periaqueductal gray (vPAG) are involved in general anesthesia and how general anesthetics affect these neurons remain sparsely documented. To determine the role of vPAG DA neurons in propofol-induced anesthesia, we performed microinjection of 6-hydroxydopamine (6-OHDA) into vPAG to damage DA neurons and investigated the alteration in somatosensory electroencephalogram (EEG), as well as the induction and recovery time of propofol anesthesia. Subsequently, we examined the effect of propofol on the electrophysiological activity of DA neurons in vPAG using whole-cell patch clamp. Two weeks after 6-OHDA microinfusion, DA neurons in the vPAG were markedly reduced by 63.6% in the 6-OHDA-treated rats compared with vehicle rats. This lesion significantly shortened the induction time (7.15 ± 3.97 s vs. 11.18 ± 2.83 s,P< 0.05) and prolonged the recovery time of propofol anesthesia (780.26 ± 150.86 s vs. 590.68 ± 107.97 s,P< 0.05). Meanwhile, EEG in somatosensory cortex revealed that delta power (0–4 Hz) was significantly higher in 6-OHDA-treated rats than vehicle rats. In the electrophysiological experiment, propofol decreased the frequency of spontaneous excitatory postsynaptic currents rather than the amplitude and decay time. In addition, propofol preferentially increased the frequency and prolonged the decay time of spontaneous inhibitory postsynaptic currents without affecting the amplitude. Significance: Propofol can promote presynaptic GABA release, inhibit presynaptic glutamate release and increase postsynaptic GABAAreceptor sensitivity, which eventually inhibits the activity of vPAG DA neurons and thereby influences the state of consciousness.