In clinical studies, stress is traditionally measured as the ability of external or internal stimuli to activate the hypothalamic-pituitary-adrenal (HPA) axis. Through activation of CRH-R1, CRH stimulates the synthesis and release of adrenocorticotropin (ACTH) by the anterior pituitary, which in turn stimulates the synthesis and release of cortisol by the adrenal cortex. Both enhanced and attenuated hormonal responses to stress are maladaptive. Chronic HPA axis dysregulation is associated with the development of mood disorders (Gold and Chrousos, 2002) and alcohol addiction (Sinha et al., 1999; Uhart et al., 2006). Studies in large cohorts of alcoholics demonstrated that 50–60% of patients simultaneously suffer from anxiety or depression disorders (Gratzer et al., 2004; Hettema et al., 2003). In approximately half of the patients, alcohol dependence preceded the manifestation of depressive or anxiety symptoms. In the other half, depression or anxiety was the primary disorder (Hettema et al., 2003). Dysregulation of the brain CRH system (innate or resulting as a maladaptive response to drugs of abuse or stress) appears to be one of the major elements common to depression, anxiety and addiction (see
