The results of our study are consistent with the findings by Treutlein and colleagues implicating two CRHR1 SNPs (rs242938 and rs1876831), distal to haplotype block 1, with increased alcohol use (Treutlein et al., 2006), particularly in the context of negative life events (Blomeyer et al., 2008). Although these studies rely on tag SNPs to capture variance in the CRHR1 gene, they emphasize the need to elucidate the molecular mechanisms underlying CRHR1 expression and function, as they may influence reactivity to stress and possibly alcoholism risk. To that end, recent studies have highlighted the role of the CRHR1 gene in alcohol use in animals (Molander et al., 2012) and in clinical samples (Ribbe et al., 2011). A notable preclinical study compared global CRHR1 knockout mice and conditional brain-specific CRHR1 knockout across a range of alcohol exposure conditions, including an alcohol deprivation paradigm that serves as a relapse analog (Molander et al., 2012). Results suggested that stress-induced augmentation of alcohol intake and escalation of alcohol intake was lower in the brain-specific knockout mice as compared to control animals. These findings indicate that
