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Insomnia-related rodent models in drug discovery

Acta Pharmacologica Sinica (2024)Cite this article

Abstract

Despite the widespread prevalence and important medical impact of insomnia, effective agents with few side effects are lacking in clinics. This is most likely due to relatively poor understanding of the etiology and pathophysiology of insomnia, and the lack of appropriate animal models for screening new compounds. As the main homeostatic, circadian, and neurochemical modulations of sleep remain essentially similar between humans and rodents, rodent models are often used to elucidate the mechanisms of insomnia and to develop novel therapeutic targets. In this article, we focus on several rodent models of insomnia induced by stress, diseases, drugs, disruption of the circadian clock, and other means such as genetic manipulation of specific neuronal activity, respectively, which could be used to screen for novel hypnotics. Moreover, important advantages and constraints of some animal models are discussed. Finally, this review highlights that the rodent models of insomnia may play a crucial role in novel drug development to optimize the management of insomnia.

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Fig. 1: Modeling of insomnia in rodents.

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Acknowledgements

This study was partly supported by the National Natural Science Foundation of China (82020108014 and 32070984 to ZLH; 82071491 and 31871072 to WMQ), the STI2030-Major Project (2021ZD0203400 to ZLH), Program for Shanghai Outstanding Academic Leaders (to ZLH), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01 to ZLH), Zhangjiang Lab, and Shanghai Center for Brain Science and Brain-Inspired Technology, Lingang Laboratory & National Key Laboratory of Human Factors Engineering Joint Grant (LG-TKN-202203-01).

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  1. These authors contributed equally: Ze-ka Chen, Yuan-yuan Liu

Authors and Affiliations

  1. Department of Pharmacology, School of Basic Medical Sciences; State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science; Joint International Research Laboratory of Sleep; and Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China

    Ze-ka Chen, Yuan-yuan Liu, Ji-chuan Zhou, Wei-min Qu & Zhi-li Huang

  2. Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA

    Ze-ka Chen

  3. Department of Neurology (Sleep Disorders), the Affiliated Chaohu Hospital of Anhui Medical University, Hefei, 238000, China

    Gui-hai Chen

  4. Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou, 215004, China

    Chun-feng Liu

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  1. Ze-ka Chen
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Correspondence to Chun-feng Liu, Wei-min Qu or Zhi-li Huang.

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Chen, Zk., Liu, Yy., Zhou, Jc. et al. Insomnia-related rodent models in drug discovery. Acta Pharmacol Sin (2024). https://doi.org/10.1038/s41401-024-01269-w

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