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

  • Glenn R. Valdez


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.


Chronic Mild Stress Inescapable Shock Acoustic Startle Response Lateral Septum CRF2 Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Adrenocorticotropic hormone




Bed nucleus of the stria terminalis


Corticotropin-releasing factor


Flinders resistant line


Flinders sensitive line


Hamilton anxiety scale


Hamilton depression scale

HPA axis

Hypothalamic-pituitary-adrenal axis


Selective serotonin reuptake inhibitor

Ucn 1

Urocortin 1

Ucn 2

Urocortin 2

Ucn 3

Urocortin 3


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© Springer India 2016

Authors and Affiliations

  1. 1.Department of PsychologyGrand Valley State UniversityAllendaleUSA

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