2009). A GeneMania (Warde-Farley et al., 2010) analysis of these 11 genes indicates that all 10 genes with positive fold changes are highly co-expressed. The two main regulators appear to be cAMP responsive element binding protein 1 (CREB1) and Tumor protein P53 (TP53). CREB1 targets 7 of the 10 upregulated genes; upstream analysis indicates CREB1 is active in vHip and mPFC (Supplemental Tables 2, 3), and the DRN (McClintick et al., 2015) and PAG (McClintick et al., 2016). TP53 targets 6 of the genes; three (Atf3, Btg2, and Npas4), along with Nr4a1and Gadd45γ, have been shown to be upregulated by calcium signaling and CREB (Tan, Zhang, Hoffmann, & Bading, 2012), and are neuroprotective (Zhang et al., 2009). Both GADD45γ and Nr4a1 are increased in all 4 brain regions, but the increases met significance in only 1 and 3 regions respectively. Atf3 is expressed at low levels in the nervous system but is induced following seizures and other stressors in the brain (Moore & Goldberg, 2011). Seven of the 10 co-expressed genes, are enriched in astrocytes (Cahoy et al., 2008). Five of these 7 (Table 6) were also increased in binge exposed adult rats (Bell et al., 2009). This could be
