CRF(2) Receptors: An Emerging Role in Anxiety

Corticotropin-releasing factor (CRF) systems are major regulators of stress-induced endocrine, autonomic, immune and behavioral responses. Studies indicate that two high affinity CRF receptors designated CRF(1) and CRF(2) mediate the actions of CRF. Dysregulation of this CRF system, which may involve excessive secretion of the CRF peptide and/or alterations in CRF receptor functions, may facilitate the occurrence of stress-induced disorders including anxiety and depression. In the last few years, several specific CRF(1) receptor antagonists were developed and shown to be effective in reducing animal anxiety and depression-like behavior. In contrast, comparable information concerning the role of the CRF(2) receptor has not been available. However, recent preclinical studies demonstrate that CRF(2) receptors may also mediate anxiety behavior. Although the involvement of both CRF(1) and CRF(2) receptors underscores the complexity and diversity in CRF receptor systems underlying the neurobiology of anxiety, the development of CRF receptor antagonists that are capable of binding to one or both receptors may lead to novel pharmacotherapies for the treatment of psychopathology.(c) 2002 Prous Science. All rights reserved.