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Orexin, Alcohol and Sleep Homeostasis

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Orexin and Sleep

Abstract

Alcoholism is a third leading preventable cause of death in the United States. One of the most significant and severe consequences of alcohol use is its effects on sleep. Strong and convincing evidences suggest that alcohol-induced sleep disruptions may have a major role towards the development of alcoholism. However, very little is known about how and where alcohol acts to affect sleep. Adenosine (AD) is strongly implicated in sleep promotion as well as in mediating alcohol-induced sleep. Since orexinergic system plays a pivotal role in the initiation and maintenance of wakefulness, we hypothesized that alcohol may act via AD to inhibit the orexinergic system and promote sleep. In this chapter, we have described a series of experiments performed on Sprague-Dawley rats to test our hypothesis. Our first group of experiments suggests that adenosinergic mechanism in the perifornical hypothalamus is involved in spontaneous as well as recovery sleep after prolonged wakefulness. Our second group of experiments suggests that alcohol increases extracellular levels of AD in the orexin-rich perifornical hypothalamus, increased AD activates A1 receptors on orexinergic neurons and inhibits them, and inhibition of orexinergic neurons may result in sleep promotion. In our third group of experiments, we have shown that alcohol withdrawal-induced sleep disruptions are associated with downregulation of orexin gene expression suggesting a crucial link between orexinergic system and alcohol induced sleep disruptions. In conclusion, the results of our studies suggest that interaction between adenosinergic mechanism and the orexinergic system in the perifornical hypothalamus is crucial for alcohol’s effects on sleep.

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Authors and Affiliations

  1. Harry S. Truman Memorial Veterans Hospital and Department of Neurology, University of Missouri, Research, Room A023, 800 Hospital Drive, Columbia, MO, 65201, USA

    Rishi Sharma, Pradeep Sahota & Mahesh M. Thakkar

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  1. Rishi Sharma
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  2. Pradeep Sahota
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  3. Mahesh M. Thakkar
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Correspondence to Mahesh M. Thakkar .

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Editors and Affiliations

  1. Dept. of Molecular Neurosci. & Integrati, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan

    Takeshi Sakurai

  2. Somnogen Canada Inc, President and Chief Executive Officer, Toronto, Ontario, Canada

    S.R. Pandi-Perumal

  3. Dept. Pharmacology & Therapeutics, Clinics Hospital Montevideo School of Medicine, Montevideo, Uruguay

    Jaime M. Monti

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Sharma, R., Sahota, P., Thakkar, M.M. (2015). Orexin, Alcohol and Sleep Homeostasis. In: Sakurai, T., Pandi-Perumal, S., Monti, J. (eds) Orexin and Sleep. Springer, Cham. https://doi.org/10.1007/978-3-319-23078-8_9

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