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Corticotropin-Releasing Factor Receptors as a Potential Target in the Developments of Antidepressant Drugs

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Abstract

Depression is a highly prevalent form of mental illness that is one of the leading causes of disability worldwide. Because stressful life events frequently trigger its symptoms, depression is often characterized as a stress-related disorder, and chronic exposure to stress has been hypothesized to lead to long-term alterations of the physiological systems thought to mediate the stress response. Understanding the biological changes resulting from chronic stress is important because these long-term modifications may underlie the symptoms of depression. The corticotropin-releasing factor (CRF) system has long been considered to be one of the body’s major regulators of the stress response. Two genes encoding distinct G-protein-coupled CRF receptors have been identified: the CRF1 receptor and CRF2 receptor. Endogenous ligands for these receptors, including CRF, urocortin 1, urocortin 2, and urocortin 3, display different binding affinities for the two CRF-receptor subtypes, as well as distinct behavioral profiles in animal models of depression and anxiety. These findings have led to the hypothesis that CRF1 and CRF2 receptors may play distinct roles in the regulation of stress-related behavior, with the CRF1 receptor underlying the activational components of the stress response and the CRF2 receptor acting as a compensatory coping mechanism. The present chapter will review the role of CRF-related ligands and CRF receptors in depression and proposes targeting the CRF system as a potential pharmacotherapy for depressive disorders.

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Abbreviations

ACTH:

Adrenocorticotropic hormone

ASVG-30:

Antisauvagine-30

BNST:

Bed nucleus of the stria terminalis

CRF:

Corticotropin-releasing factor

FRL:

Flinders resistant line

FSL:

Flinders sensitive line

HAM-A:

Hamilton anxiety scale

HAM-D:

Hamilton depression scale

HPA axis:

Hypothalamic-pituitary-adrenal axis

SSRI:

Selective serotonin reuptake inhibitor

Ucn 1:

Urocortin 1

Ucn 2:

Urocortin 2

Ucn 3:

Urocortin 3

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  1. Department of Psychology, Grand Valley State University, 1 Campus Drive, Allendale, MI, 49401, USA

    Glenn R. Valdez

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  1. Vice-Rectorate for Research and Sci, Camilo José Cela University Vice-Rectorate for Research and Sci, Madrid, Spain

    Francisco López-Muñoz

  2. International Medical Sciences Research Study Center, Sri Sathya Sai Medical Educational & Research Foundation, Coimbatore, India

    Venkataramanujam Srinivasan

  3. Department of Neurosciences and Ima, University of Chieti Department of Neurosciences and Ima, Italy, Italy

    Domenico de Berardis

  4. Department of Biomedical Sciences (Pharmacology Area), University of Alcalá, Madrid, Spain

    Cecilio Álamo

  5. Department of Neuropsychiatry, Kyushu University, Fukuoka, Japan

    Takahiro A. Kato

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Valdez, G.R. (2016). Corticotropin-Releasing Factor Receptors as a Potential Target in the Developments of Antidepressant Drugs. In: López-Muñoz, F., Srinivasan, V., de Berardis, D., Álamo, C., Kato, T. (eds) Melatonin, Neuroprotective Agents and Antidepressant Therapy. Springer, New Delhi. https://doi.org/10.1007/978-81-322-2803-5_44

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