Neuropeptide Regulation of Stress-Induced Behavior: Insights from the CRF/Urocortin Family

The neuropeptide corticotropin-releasing factor (CRF) and the more recently identified family members, the urocortins (Ucns), are proposed to integrate the neuroendocrine, autonomic, metabolic and behavioral responses to stressors. Chronic hyperactivation of the CRF system has been linked to stressrelated emotional disorders such as anxiety and depression. The intracerebral administration of CRF or Ucn1 results in behavioral responses that are similar to those observed when animals are exposed to a stressor. The behavioral effects include increased anxiety-like behavior, decreased food consumption, increased arousal, altered locomotor activity, diminished sexual behavior, and sleep disruption. The role of the CRF/Urocortin system in modulating the behavioral responses to stressors was further demonstrated based on the behavioral phenotypes of transgenic mice that overexpress, or are deficient in, the different CRF family members. The CRFeCRFR1 system is suggested as critical for initiating stress responses, while the urocortinseCRFR2 system is suggested to terminate stress responses and restore homeostasis.