Homeostasis within the corticotropin‐releasing factor system via CRF2 receptor activation: a novel approach for the treatment of anxiety

Abstract

AbstractAnxiety and depression are highly prevalent forms of mental illness that are often thought of as stress‐related disorders because their symptoms are frequently triggered by stressful life events. Clinical studies provide strong evidence for the involvement of corticotropin‐releasing factor (CRF), a key regulator of the stress response, in anxiety and depression. Recent evidence from studies involving CRF2 receptor knockout mice and CRF2 receptor‐specific ligands suggests that the two CRF receptor subtypes have a differential role in mediating the stress response, where activation of the CRF1 receptor leads to increases in the stress response and the CRF2 receptor represents a compensatory coping mechanism to oppose this action. This proposed differential regulation of stress‐related behaviors via the two CRF receptor subtypes suggests that a disruption of homeostasis within the stress system may be a key underlying factor in the regulation of psychiatric disorders associated with chronic stress. Therefore, it appears that restoring the neurochemical balance within the CRF system via CRF2 receptor activation may provide a novel approach in the treatment of stress‐related disorders. Drug Dev. Res. 65:205–215, 2005. © 2005 Wiley‐Liss, Inc.