individuals with a family history of alcoholism have lower plasma concentrations for beta-endorphin and ACTH (Gianoulakis et al., 2005), which suggests a dysfunction of the HPA-axis that may be related to genetic variation in POMC associated with alcohol dependence. In addition, the CRF brain-stress system, which plays a key role in the negative affective state and compulsive drug seeking and intake associated with protracted abstinence, is most likely engaged because mice that lack the CRF-1 receptor show a blunted ACTH response to acute alcohol (Lee et al., 2001), and fail to show dependence-induced drinking (Chu et al., 2007). SNPs within the CRF1 receptor gene (CRHR1) were associated with compulsive alcohol consumption and binge drinking phenotypes in an independent sample (Treutlein et al., 2006), further supporting a possible epistatic effect of the HPA-ACTH stress system and extra-hypothalamic CRF stress system.
