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Regulation of serotonin release by inhibitory and excitatory amino acids

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Serotonin and Sleep: Molecular, Functional and Clinical Aspects

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Abstract

Serotonergic neurons are spontaneously active with slow regular discharge during alert behavior and decreased activity during sleep. Sleep-related inhibition of serotonergic neurons is mediated by GABAergic inputs that originate in hypothalamic and brainstem sleep centers. During alert behavior, tonic release of GABA contributes to feedback and feedforward inhibitory circuits that, together with serotonin autoreceptors, prevent excess stimulation of serotonergic neurons. Glutamatergic inputs to the raphe originate in the brainstem, several hypothalamic nuclei and cerebral cortex. Although glutamate receptor agonists strongly stimulate serotonergic neuronal discharge, the physiological significance of glutamatergic inputs is not well established. In the dorsal raphe nucleus (DRN), more glutamatergic fibers terminate on GABAergic than serotonergic neurons. Moreover, GABA normally restrains the excitatory influence of glutamatergic inputs to serotonergic neurons in the DRN. Peptidergic neurons modulate the activity of GABAergic and glutamatergic interneurons that synapse with serotonergic neurons in the DRN. These neuropeptides, for example CRF, endogenous opioids and Substance P, are implicated in responses to environmental challenges. Thus, stress can indirectly influence the activity of serotonergic neurons. In the raphe, GABAergic and glutamatergic interneurons may serve as a final common pathway for integrating information about environmental challenges and inputs from hypothalamic and brainstem centers that control the usual sleep-related inhibition of serotonergic neurons. Neuropeptides might thereby promote alert behavior to appropriately cope with stress. However, persistent peptidergic-induced changes in the strength of GABAergic and glutamatergic inputs to serotonergic neurons could contribute to insomnia, anxiety and major psychiatric disorders such as depression and schizophrenia.

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Authors and Affiliations

  1. Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, 604 Allison Road, Piscataway, NJ, 08854, USA

    Sidney B. Auerbach

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  1. Sidney B. Auerbach
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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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Auerbach, S.B. (2008). Regulation of serotonin release by inhibitory and excitatory amino acids. 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_10

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