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Stress-related Serotonergic Systems: Implications for Symptomatology of Anxiety and Affective Disorders

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Abstract

Previous studies have suggested that serotonergic neurons in the midbrain raphe complex have a functional topographic organization. Recent studies suggest that stimulation of a bed nucleus of the stria terminalis-dorsal raphe nucleus pathway by stress- and anxiety-related stimuli modulates a subpopulation of serotonergic neurons in the dorsal part of the dorsal raphe nucleus (DRD) and caudal part of the dorsal raphe nucleus (DRC) that participates in facilitation of anxiety-like responses. In contrast, recent studies suggest that activation of a spinoparabrachial pathway by peripheral thermal or immune stimuli excites subpopulations of serotonergic neurons in the ventrolateral part of the dorsal raphe nucleus/ventrolateral periaqueducal gray (DRVL/VLPAG) region and interfascicular part of the dorsal raphe nucleus (DRI). Studies support a role for serotonergic neurons in the DRVL/VLPAG in inhibition of panic-like responses, and serotonergic neurons in the DRI in antidepressant-like effects. Thus, data suggest that while some subpopulations of serotonergic neurons in the dorsal raphe nucleus play a role in facilitation of anxiety-like responses, others play a role in inhibition of anxiety- or panic-like responses, while others play a role in antidepressant-like effects. Understanding the anatomical and functional properties of these distinct serotonergic systems may lead to novel therapeutic strategies for the prevention and/or treatment of affective and anxiety disorders. In this review, we describe the anatomical and functional properties of subpopulations of serotonergic neurons in the dorsal raphe nucleus, with a focus on those implicated in symptoms of anxiety and affective disorders, the DRD/DRC, DRVL/VLPAG, and DRI.

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Acknowledgments

The project described was supported by R01MH086539 (CAL) and R01MH065702 (AS/CAL) from the National Institute of Mental Health and Grant No. 0845550 (CAL) from the National Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Mental Health, the National Institutes of Health, or the National Science Foundation.

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Authors and Affiliations

  1. Department of Integrative Physiology and Center for Neuroscience, University of Colorado Boulder, Boulder, CO, 80309-0354, USA

    Christopher A. Lowry

  2. School of Psychological Science, La Trobe University, Melbourne, 3086, Australia

    Matthew W. Hale

  3. Department of Psychiatry and Pharmacology & Toxicology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA

    Anantha Shekhar

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  1. Matthew W. Hale
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  2. Anantha Shekhar
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  3. Christopher A. Lowry
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Correspondence to Christopher A. Lowry.

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Hale, M.W., Shekhar, A. & Lowry, C.A. Stress-related Serotonergic Systems: Implications for Symptomatology of Anxiety and Affective Disorders. Cell Mol Neurobiol 32, 695–708 (2012). https://doi.org/10.1007/s10571-012-9827-1

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  • DOI: https://doi.org/10.1007/s10571-012-9827-1

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