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Dopamine D1 Receptor in the Nucleus Accumbens Modulates the Emergence from Propofol Anesthesia in Rat

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Abstract

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.

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Acknowledgements

An early version of this manuscript was presented in the Best of Abstracts (Basic Science) session in the American Society Anesthesiologists (ASA) annual meeting 2019. We thank all individuals who took part in this research.

Funding

This research was supported by grants from the National Natural Science Foundation of China (NSFC, Grant Nos. 81560237 and 81860204).

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Author notes

  1. Yi Zhang and Huan Gui are first authors.

Authors and Affiliations

  1. Department of Anesthesiology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China

    Yi Zhang, Jie Zhang & Chengxi Liu

  2. Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, China

    Yi Zhang & Xiaoli Liang

  3. Guizhou Key Laboratory of Brain Science, Guizhou Key Laboratory of Anesthesia and Organ Protection, The Affiliated Hospital of Zunyi Medical University, Zunyi, China

    Yi Zhang, Huan Gui, Zikun Duan, Tian Yu, Jie Zhang, Xiaoli Liang & Chengxi Liu

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Zhang, Y., Gui, H., Duan, Z. et al. Dopamine D1 Receptor in the Nucleus Accumbens Modulates the Emergence from Propofol Anesthesia in Rat. Neurochem Res 46, 1435–1446 (2021). https://doi.org/10.1007/s11064-021-03284-3

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