genes having lower expression. A second cluster of pathways includes synaptic long term potentiation (LTP) and several signaling pathways, including those related to dopamine regulation of cAMP signaling and nNOS; these pathways also show reduced activity. Very closely related to these pathways, with some key overlapping genes, are pathways of cAMP and G-Protein signaling, which contain a cluster of protein kinases and phosphatases (Prkcg, Gsk3b, Ppp3r2, Ppp1r14a) that are decreased in expression. Protein kinase A signaling, which overlaps with both the Wnt and cAMP groups, has an overall neutral z-score, but most differentially expressed genes in that pathway are decreased. Protein kinase A signaling is initiated by multiple G-protein coupled receptors and has many different downstream targets, some of which are increased (e.g. tyrosine hydroxylase) and others decreased (e.g. eNOS / Nos3 and Gsk3β) (Tables 2, 3). Four pathways involved in phosphoinositide metabolism have a completely overlapping set of genes, all decreased in expression; these include a different group of phosphatases (Ppp1r12c, Ppp1r13b, Ptpn23). Pathways related to fibrosis contain a set of collagens that are all expressed at lower levels in the binge-drinking animals. Some genes, including Crebbp, Prkcg, Gsk3b, Ppp3r2, Nfkbia, Dusp1 and Calm1, are shared across the different
