Effects of urocortins on stress responses are more restricted but also more complex than those of CRF. In contrast to CRF, urocortins do not play a direct role in HPA axis responses (Kageyama et al., 2003; Nemoto et al., 2009). Ucn/CRF2R activation has repeatedly been shown to result in reduction of anxiety-like behavior (anxiolysis) and recovery from stress (Coste et al., 2000; Tanaka and Telegdy, 2008; Todorovic et al., 2007; Valdez et al., 2003), i.e. effects opposite those mediated by CRF through actions at CRF1 receptors. However, CRF2R signaling can also drive stress-induced increases in anxiety (Henry et al., 2006), aversion (Land et al., 2008), and alcohol consumption (Pastor et al., 2011), while social defeat stress potently activates CRF2R expressing neurons of the medial amygdala (Fekete et al., 2009). Urocortins also play a role in long-term stress adaptation (Neufeld-Cohen et al., 2010a; Neufeld-Cohen et al., 2010b). It is clear from the complexity of functional consequences that Ucn/CRF2R signaling does not serve simply as an “anti-alarm” system opposing CRF actions.
