Contribution of Urocortin to the Development of Excessive Drinking

The corticotropin-releasing factor (CRF) system plays a role in alcohol consumption, and its dysregulation can contribute to alcohol use disorder. This system includes four peptide ligands: CRF, urocortin (Ucn)1, Ucn2, and Ucn3. Historically, attention focused on CRF, however, Ucn1 also plays a critical role in excessive alcohol use. This review covers evidence for this contribution and contrasts the role of Ucn1 with CRF. While CRF can promote binge consumption, this regulation occurs through generalized mechanisms that are not specific for alcohol. In contrast, inhibition of Ucn1 action specifically blunts escalation of alcohol drinking. Lesions, genetic knockout, and RNA interference experiments indicate that the centrally projecting Edinger-Westphal nucleus is the neuroanatomical source of Ucn1 critical for alcohol drinking. We propose that the contributions of Ucn1 to excessive drinking likely occur through enhancing rewarding properties of alcohol and symptoms of alcohol withdrawal, whereas CRF drives dependence-induced drinking at later stages of alcohol use. The transition from occasional binge drinking to dependence intricately depends on CRF system plasticity and coordination of CRF and Ucn1.