In summary, motivational mechanisms that mediate the role of Ucn peptides and CRF2 receptor activation on alcohol consumption are presently less well understood than those of CRF1Rs and may involve both stress- and reward-related mechanisms. The relative contribution of individual urocortins in different brain regions, and in different stages of addiction-related processes, also remains to be established. More work is needed to assess the potential of CRF2R ligands as alcoholism pharmacotherapies, determine in what stage of the disease process they may be most useful, and define their optimal pharmacological profile. Due to the bi-directional effects of CRF2R agonists on alcohol consumption, region-specific manipulations of endogenous urocortins will be required to dissect their relative involvement in motivation to seek and consume alcohol and in the transition to alcohol dependence.
