Converging lines of evidence indicate that endogenous Ucn1 promotes alcohol consumption (Bachtell et al., 2003; Giardino et al., 2011a; Ryabinin et al., 2012; Ryabinin and Weitemier, 2006). In rodents, Ucn1-containing neurons within the cerntrally-projecting Edinger-Westphal nucleus (EWcp) are particularly sensitive to voluntary alcohol consumption (Anacker et al., 2011; Bachtell et al., 2003; Kaur and Ryabinin, 2010; Ryabinin et al., 2003; Weitemier et al., 2001). The neuropeptide-containing neurons of the EWcp send Ucn1-positive axons to brain regions that include the lateral septum and doral raphe nucleus, structures involved in behavioral stress responses (Bachtell et al., 2004; Bittencourt et al., 1999; Kozicz et al, 2011). In analyses of rodent strains that differ in alcohol-related traits, greater levels of EWcp-Ucn1 protein were associated with greater alcohol consumption and alcohol-induced reward (Bachtell et al., 2003; Fonareva et al., 2009; Kiianmaa et al., 2003; Ryabinin and Weitemier, 2006; Turek et al., 2005). A recent comparison of alcohol-preferring C57BL/6J mice and alcohol-avoiding DBA/2J mice showed that in these lines, differences in Ucn1 peptide levels were due to increased EWcp-Ucn1 mRNA levels (Giardino et al., 2012a).
