accumbens following chronic cocaine exposure (Ang et al., 2001). These studies demonstrate that NFκB signaling pathways are regulated in the brain by drugs of abuse. To date, only 1 functional study for immune pathways in the brain in drug responses has been done, implicating NFκB in cocaine reward in the accumbens (Russo et al., 2009). Our microarray study detected a marked up-regulation of genes in the innate immune signaling pathways Tl and Imd following acute ethanol exposure. Both Tl and Imd pathways converge on members of the NFκB family, indicating that regulation of NFκB signaling by ethanol is an evolutionarily conserved phenomenon. Preliminary behavioral analysis of flies carrying a transposon insertion in the NFκB homolog Rel locus has suggested that Rel may regulate ethanol sedation sensitivity (Table S6). This suggests that Rel, and by extension the Imd pathway, contributes to ethanol responses in flies. As these signaling pathways are used in many contexts during development and in postembryonic physiology, it will be important to map their actions in space and time to pinpoint their function in ethanol behavioral responses.
