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Circadian control by serotonin and melatonin receptors: Clinical relevance

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Serotonin and Sleep: Molecular, Functional and Clinical Aspects

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Abstract

This chapter reviews the role of the different serotonin receptors located in the circadian apparatus and their possible clinical implications for the activity of antidepressants. The central oscillator located in the hypothalamic suprachiasmatic nuclei (SCN) received three major inputs: (a) the retinohypothalamic tract, which extends from the retina and releases glutamate and pituitary adenylate cyclase-activating polypeptide at its nerve endings; (b) the geniculohypothalamic tract, which originates in the retino-recipient area of the intergeniculate leaflet (IGL) and releases neuropeptide Y and Γ-aminobutyric acid as transmitters; (c) a dense serotonergic innervation arising from ascending projections of serotonin neurons in midbrain raphe nuclei. Serotonergic projections come directly from the median raphe nucleus and indirectly from the dorsal raphe nucleus via the IGL. Destruction of serotonergic afferents to the SCN modifies circadian behavioral responses to light. At the SCN several serotonin receptors are localized (i.e., 5-HT1A, 5-HT1B, 5-HT2A, 5-HT2C, 5-HT5A and 5-HT7 receptor subtypes). Basic and clinical data on the efficacy of agomelatine, a novel antidepressant that combines a potent agonist activity of melatonin MT1 and MT2 receptors and an antagonist activity of 5-HT2C receptors, are reviewed.

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Author information

Authors and Affiliations

  1. Departmento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, 1121, Buenos Aires, Argentina

    Daniel P. Cardinali

  2. Comprehensive Center for Sleep Medicine, Division of Pulmonary, Critical Care and Sleep Medicine, Mount Sinai School of Medicine, 1176 - 5th Avenue, New York, NY, 10029, USA

    Seithikurippu R. Pandi-Perumal

  3. Department of Physiology, School of Medical Sciences, University Sains Malaysia, Kubang kerian, Kota Bharu, Kelantan, Malaysia

    Venkataramanujan Srinivasan

Authors
  1. Daniel P. Cardinali
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  2. Seithikurippu R. Pandi-Perumal
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  3. Venkataramanujan Srinivasan
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Editor information

Editors and Affiliations

  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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Cardinali, D.P., Pandi-Perumal, S.R., Srinivasan, V. (2008). Circadian control by serotonin and melatonin receptors: Clinical relevance. 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_19

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