Our results demonstrate the validity of convergent genomic analyses to nominate genes that might be important for genetic regulation of complex behaviors. The subtlety of such regulation is emphasized by the observation that although three different tests of alcohol consumption show effects of deletion of some of the genes, only the 24 hr two-bottle choice test, which was the primary basis of gene selection, showed effects of all six genes. In addition, our findings indicate a novel and unexpected role for proinflammatory signaling in regulation of alcohol consumption. Although the brain proinflammatory system has most often been studied in relation to neuropathology, emerging evidence shows that it represents a signaling network that regulates normal behavior (Boulanger, 2009; Rihel et al., 2010). Our results raise the possibility that rewarding (or aversive) effects of alcohol may be determined by cytokine signaling. This may be related to the observation that activation of cytokine signaling (e.g., by lipopolysaccharide) produces a ‘sickness’ behavior that includes decreases in reward function (measured by intracranial self-stimulation) (Borowski et al., 1998; Henry et al., 2008) similar to that observed
