post-acute withdrawal) (O’Dell et al., 2004; Rimondini et al., 2002). Intracerebroventricular administration of a CRF1/CRF2 antagonist blocked the dependence-induced increase in ethanol self-administration during both acute withdrawal and protracted abstinence (Valdez et al., 2004). When administered directly into the central nucleus of the amygdala, a CRF1/CRF2 antagonist blocked ethanol self-administration in ethanol-dependent rats (Funk et al., 2006, 2007). Systemic injections of small-molecule CRF1 antagonists also blocked the increased ethanol intake associated with acute withdrawal (Knapp et al., 2004; Overstreet et al., 2004; Funk et al., 2007). These data suggest an important role for CRF, primarily within the central nucleus of the amygdala, in mediating the increased self-administration associated with dependence.
