Review Article

Insomnia-related rodent models in drug discovery

Ze-ka Chen1,2,3,4,5, Yuan-yuan Liu1,2,3,4, Ji-chuan Zhou1,2,3,4, Gui-hai Chen6, Chun-feng Liu7, Wei-min Qu1,2,3,4, Zhi-li Huang1,2,3,4
1 Department of Pharmacology, School of Basic Medical Sciences
2 State Key Laboratory of Medical Neurobiology, Institutes of Brain Science and Collaborative Innovation Center for Brain Science
3 Joint International Research Laboratory of Sleep
4 and Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
5 Department of Pharmacology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
6 Department of Neurology (Sleep Disorders), the Affiliated Chaohu Hospital of Anhui Medical University, Hefei 238000, China
7 Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China
Correspondence to: Chun-feng Liu: liuchunfeng@suda.edu.cn, Wei-min Qu: quweimin@fudan.edu.cn, Zhi-li Huang: huangzl@fudan.edu.cn,
DOI: 10.1038/s41401-024-01269-w
Received: 9 November 2023
Accepted: 24 March 2024
Advance online: 26 April 2024

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.
Keywords: rodent models; insomnia; drug discovery; hypnotics; sleep–wake profile

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