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Serotonin and Sleep: Molecular, Functional and Clinical Aspects pp 325–369Cite as

Involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking

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Abstract

The involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking is complex due to a multitude of presynaptic and/or postsynaptic actions also involving other neurotransmitter systems. Both receptors produce an important inhibitory feed back to the serotonergic raphe neurons. Overall, most studies support the possibility that stimulation of postsynaptic 5-HT1A receptors, e.g., via systemic administration of a high dose of agonists increases wakefulness and decreases sleep. Local administration of agonists in dorsal raphe nucleus mainly produces a response similar to the “low-dose” systemic administration, decreasing wakefulness and increasing rapid eye movement (REM) sleep via disinhibition of mesopontine REM sleep promoting neurons. Systemic administration of 5-HT1B receptors agonists consistently increases wakefulness and decreases REM sleep, as do the 5-HT1A agonists. The mechanism by which 5-HT1B receptors affect state modulation remain elusive. The general arousing effects of 5-HT1A and 5-HT1B agonists should also be considered in relation to the multiple, largely redundant, neurotransmitter systems that maintain arousal. Finally, 5-HT1A and 5-HT1B receptor are important modulators of the circadian rhythm largely by affecting the response of the suprachiasmatic nucleus to light and the secretion of melatonin from the pineal gland. The development of more selective ligands seems crucial to further explore the role of these receptors in state modulation.

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  1. Department of Biomedicine, University of Bergen, Jonas Lies vei 91, 5009, Bergen, Norway

    Chiara M. Portas & Janne Grønli

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  1. Chiara M. Portas
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  1. Pharmacology and Therapeutics, School of Medicine, Clinics Hospital, Montevideo, 11300, Uruguay

    Jaime M. Monti

  2. Division of Clinical Pharmacology and Experimental Therapeutics, Department of Medicine, College of Physicians and Surgeons of Columbia University, 630 West 168th Street - Rm # BB813, New York, NY, 10032, USA

    S. R. Pandi-Perumal

  3. Green Hall, Program in Neuroscience, Princeton University, Princeton, NJ, 08540, USA

    Barry L. Jacobs

  4. Psychopharmacology Unit, Dorothy Hodgkin Building Whitson Street, Bristol, BS1 3NY, UK

    David J. Nutt

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Portas, C.M., Grønli, J. (2008). Involvement of the 5-HT1A and the 5-HT1B receptor in the regulation of sleep and waking. In: Monti, J.M., Pandi-Perumal, S.R., Jacobs, B.L., Nutt, D.J. (eds) Serotonin and Sleep: Molecular, Functional and Clinical Aspects. Birkhäuser Basel. https://doi.org/10.1007/978-3-7643-8561-3_13

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