The corticotrophin releasing hormone (CRH), also referred to as corticotrophin releasing factor (CRF), is a peptidergic system that has long been proposed to be involved in drug addiction and alcoholism (Dave and Eskay, 1986; Hawley et al., 1994; Inder et al., 1995; Koob, 1999; Rivier et al., 1984; Wand and Dobs, 1991; Wilkins and Gorelick, 1986). In mammals this system is composed of four endogenous ligands, namely, corticotropin–releasing factor, Urocortin (Ucn)1, Ucn 2, and Ucn 3 (Bale and Vale, 2004). CRF and Ucn 1 are known to act on CRF1 receptors, CRF2 receptors, and/or the CRF-binding protein. CRF has greater affinity for the CRF1 receptor than for the CRF2 receptor whereas Ucn 1 acts at CRF1 receptors and CRF2 receptors with equal affinity. Ucn 2 and Ucn 3 act preferentially at CRF2 receptors (Bale and Vale, 2004). Discovered first of the four ligands, CRF has attracted most attention in the addiction field. However, evidence is accumulating that Ucn 1 also may be important for addiction-related behaviors, specifically, for alcohol self-administration (Ryabinin and Weitemier, 2006).
