Numerous studies involving rodent models have shown that such changes in brain CRF activity have important ramifications regarding alcohol self-administration behavior. For example, CRF infusion into the ventricles was shown to reduce voluntary alcohol intake in rats (Bell et al., 1998; Thorsell et al., 2005b). Likewise, transgenic CRF over-expressing mice exhibited reduced voluntary alcohol intake compared to non-transgenic controls (Palmer et al., 2004), while CRF deficient mice showed the opposite effect – increased alcohol drinking (Olive et al., 2003). Differences in brain CRF content have been observed in alcohol-naïve rats and mice known to differ in voluntary alcohol intake (Ehlers et al., 1992; George et al., 1990), although a recent report indicated no difference in brain regional expression of CRF between C57BL/6J (high alcohol drinking) and DBA/2J (low alcohol drinking) mice (Hayes et al., 2005). Additional studies in humans, monkeys, and rats suggest an association between genetic variants (single nucleotide polymorphisms) of the CRF and CRF1 receptor genes and alcohol drinking (Barr et al., 2009; Barr et al., 2008; Blomeyer et al., 2008; Hansson et al., 2006; Schmid et al.,
