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Ethanol Induces Sedation and Hypnosis via Inhibiting Histamine Release in Mice

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Abstract

Ethanol is one of the most highly abused psychoactive compounds worldwide and induces sedation and hypnosis. The histaminergic system is involved in the regulation of sleep/wake function and is a crucial player in promoting wakefulness. To explore the role and mechanism of the histaminergic system in ethanol-induced sedation and hypnosis, we recorded locomotor activity (LMA) and electroencephalography (EEG)/electromyography (EMG) in mice using an infrared ray passive sensor recording system and an EEG/EMG recording system, respectively, after administration of ethanol. In vivo microdialysis coupled with high performance liquid chromatography and fluorometry technology were used to detect histamine release in the mouse frontal cortex (FrCx). The results revealed that ethanol significantly suppressed LMA of histamine receptor 1 (H1R)-knockout (KO) and wild-type (WT) mice in the range of 1.5–2.5 g/kg, but suppression was remarkably stronger in WT mice than in H1R-KO mice. At 2.0 and 2.5 g/kg, ethanol remarkably increased non-rapid eye movement sleep and decreased wakefulness, respectively. Neurochemistry experimental data indicated that ethanol inhibited histamine release in the FrCx in a dose-dependent manner. These findings suggest that ethanol induces sedation and hypnosis via inhibiting histamine release in mice.

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Acknowledgements

This work was supported in part by grants from the National Natural Science Foundation of China (81671318 and 81171255 to ZYH) and the Programs for Science and Technology Development of Anhui Province (1501041157 to ZYH).

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  1. Zhangqing Ma and Wusan Wang have contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Quantitative Pharmacology, Department of Pharmacology, Wannan Medical College, Wuhu, 241002, China

    Zhangqing Ma, Wusan Wang & Zongyuan Hong

  2. Department of Pharmacology, School of Basic Medical Sciences, and State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science, Fudan University, Shanghai, 200032, China

    Tianxiao Wang, Wei Xu, Weiming Qu & Zhili Huang

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Contributions

ZYH and ZLH designed the experiments and guided the writing of this article. ZQM, WSW, TXW and WX were responsible for performing experiments and writing the manuscript. WMQ contributed to acquire and analyze the data. Authors included in this article agreed with the final manuscript.

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Correspondence to Zhili Huang or Zongyuan Hong.

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Ma, Z., Wang, W., Wang, T. et al. Ethanol Induces Sedation and Hypnosis via Inhibiting Histamine Release in Mice. Neurochem Res 44, 1764–1772 (2019). https://doi.org/10.1007/s11064-019-02813-5

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  • DOI: https://doi.org/10.1007/s11064-019-02813-5

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