rats.(Hansson et al. 2006) Rodents (not limited to those bred for ethanol preference) experience a prolonged period of increased anxiety and stress responsivity when withdrawn from ethanol after having been made dependent, symptoms that can be blocked by administration of a CRF1 antagonist (Sommer et al. 2008). In these animals, upregulation of CRHR1 expression has been found in the basolateral and medial amygdalar nuclei (Sommer et al. 2008) as have elevated CRF levels in their central amygdalar nucleus. In rats previously dependent on ethanol (similar findings have been reported with heroin and cocaine) (Shaham et al. 2000), relapse can be induced by foot-shock stress. For each drug, this reinstatement can be blocked by intracerebroventricular infusion of CRF1 antagonists (Le et al. 2000; Shaham et al. 2000). Direct CRF administration into involved brain regions also induces relapse in these animals (Le et al. 2000) and has been shown to block the increase in c-fos expression in the central nucleus of the amygdala that follows footshock (Funk et al. 2003).
