Together these data highlight the possible involvement of distal regions of the Crhr1 promoter as putative sites of stress-related regulation of CRF1 expression, and point to the identification of the molecular mechanisms by which the variant A alleles may confer increased sensitivity to stress and CRF1 modulation of alcohol self-administration as an important focus to uncover new therapeutic avenues for alcohol dependence. The gene discussed is CRHR1; the disease is alcohol dependence.