A large body of evidence has emerged indicating that CRF plays a critical role in alcohol (and other drug) addiction (Heilig and Koob, 2007; Koob and Zorrilla, 2010; Lowery and Thiele, 2010; Zorrilla et al., 2014). Aside from producing long-lasting dysregulation of HPA function, chronic alcohol exposure produces time-dependent changes in extracellular levels of extra-hypothalamic CRF during withdrawal (Merlo Pich et al., 1995; Olive et al., 2002; Zorrilla et al., 2001). Changes in CRF activity resulting from chronic alcohol exposure (increased CRF release along with an up-regulation in CRF1 receptors) within the extended amygdala network is thought be key to the emergence of withdrawal symptoms reflective of a negative emotional state associated with alcohol dependence. For example, increased behavioral measures of anxiety associated with alcohol withdrawal is reduced by systemic (Breese et al., 2005; Sommer et al., 2008) and central (Baldwin et al., 1991; Rassnick et al., 1993; Valdez et al., 2003) administration of CRF receptor antagonists. This effect appears to be mediated by CRF1 receptors (Overstreet et al., 2004), although a role for CRF2 receptors cannot be ruled out
