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Involvement of Ventral Periaqueductal Gray Dopaminergic Neurons in Propofol Anesthesia

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Abstract

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 GABAA receptor sensitivity, which eventually inhibits the activity of vPAG DA neurons and thereby influences the state of consciousness.

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Acknowledgements

The present work was supported by grants from the National Natural Science Foundation of China (NSFC, Grant Nos. 81560237).

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Authors and Affiliations

  1. Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi, 563000, China

    Jia Li, Tian Yu, Fu Shi, Yu Zhang, Zikun Duan, Bao Fu & Yi Zhang

  2. Department of Anesthesiology, The First Affiliated Hospital of Xi’an Medical College, No. 48 Fenghao West Road, Xi’an, 710077, China

    Jia Li

  3. Department of Anesthesiology, Affiliated Hospital of Zunyi Medical College, Zunyi, 563000, China

    Tian Yu & Yi Zhang

  4. Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi, 563000, China

    Bao Fu

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  1. Jia Li
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  2. Tian Yu
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  3. Fu Shi
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  4. Yu Zhang
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Correspondence to Yi Zhang.

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Li, J., Yu, T., Shi, F. et al. Involvement of Ventral Periaqueductal Gray Dopaminergic Neurons in Propofol Anesthesia. Neurochem Res 43, 838–847 (2018). https://doi.org/10.1007/s11064-018-2486-y

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  • DOI: https://doi.org/10.1007/s11064-018-2486-y

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