On the role of urocortin 1 in the non-preganglionic Edinger–Westphal nucleus in stress adaptation

The discovery of novel members of the CRF neuropeptide family, urocortin 1 (Ucn1), urocortin 2 and 3 has provided important insights into stress adaptation pathways, and predicted that stress adaptation involves more systems than the HPA-axis alone. This mini-review aims to summarize our recent data and research by others indicating that an important role is played by Ucn1 in the non-preganglionic Edinger–Westphal nucleus (npEW). These results point to an intriguing possibility that CRF/Ucn1 neuronal circuits comprise two separate, but functionally interrelated entities, which are coordinately regulated by acute stressors, but are inversely coupled during chronic stress. Such collaboration between the two systems would implicate a very important role of Ucn1 in adaptation to stress, and, as a consequence, in stress-related disorders like anxiety, major depression and use of drugs of abuse.