A role for corticotropin releasing factor and urocortin in behavioral responses to stressors

Corticotropin-releasing factor (CRF) and CRF-related neuropeptides have an important role in the central nervous system to mediate behavioral response s to stressors, CRF receptor antagonists are very effective in reversing st ress-induced suppression and activation in behavior. An additional CRF-like neuropeptide, urocortin, has been identified in the brain and has a high a ffinity for the CRF-2 receptor in addition to the CRF-1 receptor. Urocortin has many of the effects of CRF but also is significantly more potent than CRF in decreasing feeding in both meal-deprived and free-feeding rats. In m ouse genetic models, mice over-expressing CRF show anxiogenic-like response s compared to wild-type mice, and mice lacking the CRF-1 receptor showed an anxiolytic-like behavioral profile compared to wild-type mice. Results to date have led to the hypothesis that CRF-1 receptors may mediate CRF-like n europeptide effects on behavioral responses to stressors, but CRF-2 recepto rs may mediate the suppression of feeding produced by CRF-Like neuropeptide s. Brain sites for the behavioral effects of CRF include the locus coeruleu s (LC), paraventricular nucleus (PVN) of the hypothalamus, the bed nucleus of the stria terminalis (BNST), and the central nucleus of the amygdala. CR F may also be activated during acute withdrawal from all major drugs of abu se, and recent data suggest that CRF may contribute to the dependence and v ulnerability to relapse associated with chronic administration of drugs of abuse. These data suggest that CRF systems in the brain have a unique role in mediating behavioral responses to diverse stressors. These systems may b e particularly important in situations were an organism must mobilize not o nly the pituitary adrenal system, but also the central nervous system in re sponse to environmental challenge. Clearly, dysfunction in such a fundament al brain-activating system may be the key to a variety of pathophysiologica l conditions involving abnormal responses to stressors such as anxiety diso rders, affective disorders, and anorexia nervosa. (C) 1999 Elsevier Science B.V. All rights reserved.