The central administration of a CRF antagonist attenuates both EtOH self-administration and the anxiety-like response to stress observed during alcohol abstinence (Valdez et al. 2002) and administration of a CRFR antagonist into the CeA reverses the anxiogenic-like effect of alcohol (Rassnick et al. 1993). Rats tested 3–5 weeks post alcohol withdrawal showed an anxiogenic-like response provoked by a mild restraint stress only in rats with a history of alcohol dependence. This stress-induced anxiogenic-like response was reversed by a competitive CRF1R antagonist (Valdez et al. 2003). The increased self-administration of alcohol observed during protracted abstinence also was blocked by a competitive CRF1R antagonist (Valdez et al. 2003). Gehlert et al. (2007) also described that a novel CRF1R antagonist, the 3-(4-Chloro-2-morpholin-4-yl-thiazol-5-yl)-8-(1-ethylpropyl)-2,6-dimethyl-imidazo[1,2-b]pyridazine (MTIP) has advantageous properties for both clinical development and in preclinical alcoholism models. MTIP dose-dependently reversed anxiogenic effects of EtOH withdrawal, and blocked excessive alcohol self-administration in Wistar rats with a history of dependence (Gehlert et al. 2007). CRF also contributes to increased alcohol consumption in dependent animals, because increased EtOH self-administration is reduced by CRF1R antagonists in dependent animals but
