Table 3.

Networks identified by Ingenuity Pathway Analysis of significant differences in genes with higher or lower expression in the AcbSh and CeA of the P, HAD1, HAD2, AA and sP lines compared to their respective low ethanol consuming lines

AcbSh
Line-pair	Canonical Pathway	Higher gene expression	Lower gene expression
HAD2- LAD2	ILK Signaling	9 genes: Map2k6, Pik3ca, Pik3c2a, Pik3r1, Vim, Myl9, Vegfb, Ppp1r12a, Rps6ka5	6 genes: Mapk8, Rhog, Rnd3, Pik3c3, Rsu1, Acta1
P-NP	cAMP-mediated signaling	19 genes: Camk2d, Htr7, Atf4, Cnr1, Rapgef3, Pde8a, Pkib, Rps6ka1, Camk2g, Akap12, Pde4a, Chrm3, Ppp3cb, Adcy8, Adcy2, Adcy6, Crhr1, Gabbr2, Pth1r	36 genes: Mapk1, Grm3, Camk2a, Adcy5, Ppp3r1, Rgs14, Pde2a, Grm8, Pde10a, Rgs4, Grm4, Drd2, Mc4r, Grm7, Pde1b, Pkig, Grm2, Camk4, Htr4, Chrm4, Htr1d, Pde1a, Hrh3, Akap11, Vipr1, Map2k1, Ppp3ca, Akap5, Npy1r, Prkar2b, Oprk1, Adra2c, Htr1f, Pde8b, Adora2a, Akap1
P-NP	G-Protein Coupled Receptor Signaling	40 genes: Gpr37, Htr7, Atf4, Cnr1, Sstr1, Npy5r, Pde8a, Hcrtr1, Rps6ka1, Camk2g, Fzd1, Gprc5b, Pik3c3, Adcy6, Crhr1, Gpr64, Pth1r, Ntsr1, Gpr162, Casr, Gpr116, Camk2d, Adra1b, Grm1, Rapgef3, Hcrtr2, Cxcr7, Nfkbie, Pde4a, Nfkb1, Chrm3, Tacr1, Nfkbia, Smo, Adcy8, Adcy2, Trhr, Ednrb, Gabbr2, Plcb4	52 genes: Grm3, Gpr149, Camk2a, Pde2a, Grm8, Lphn3, Grm7, Pde1b, Fyn, Gpr12, Htr4, Ptk2b, Chrm4, Htr1d, Hrh3, Vipr1, Gpr155, Pik3r2, Bai2, Htr2a, Prkcg, Grm5, Rasgrp1, Adora2a, Prkcb, Mapk1, Pthlh, Pdpk1, Adcy5, Mras, Rgs14, Bai3, Pde10a, Rgs4, Grm4, Drd2, Mc4r, P2ry1, Grm2, Camk4, Pde1a, Map2k1, Npy1r, Gpr88, Gipr, Prkar2b, Sstr2, Oprk1, Calcr, Adra2c, Htr1f, Pde8b
P-NP	Synaptic Long Term Potentiation	12 genes: Gria4, Camk2d, Ppp3cb, Atf4, Adcy8, Ppp1r14c, Grm1, Ppp1r14a, Rapgef3, Plcb4, Rps6ka1, Camk2g	24 genes: Grm2, Camk4, Mapk1, Grm3, Gria1, Camk2b, Camk2a, Ppp1r7, Ppp3r1, Mras, Map2k1, Ppp3ca, Grm8, Gria2, Itpr1, Grm4, Prkcg, Grm7, Grm5, Prkar2b, Ppp1r12a, Prkch, Gria3, Prkcb
P-NP	Glutamate Receptor Signaling	6 genes: Slc17a6, Grm1, Grip1, Gria4, Gng2, Grik1	16 genes: Grm2, Camk4, Grm3, Grm8, Gls, Gria1, Gria2, Slc1a3, Grm4, Gng7, Grm5, Grm7, Dlg4, Grik2, Homer1, Gria3
P-NP	Protein Kinase A Signaling	28 genes: Dusp15, Camk2d, Atf4, Cdc16, Cdc25a, Ppp1r14c, Ptprd, Ppp1r14a, Gng3, Pde8a, Pygm, Dusp19, Gng2, Camk2g, Anapc2, Akap12, Nfkbie, Pde4a, Nfkb1, Nfkbia, Ppp3cb, Smo, Tgfb2, Adcy8, Adcy2, Adcy6, Pygb, Plcb4	37 genes: Mapk1, Ptpla, Ptk2, Gnb4, Camk2b, Camk2a, Ppp1r7, Adcy5, Ppp3r1, Ryr3, Ptpre, Pde2a, Pde10a, Ppp1r1b, Ptpn18, Itpr1, Pde1b, Tgfb3, Ppp1r12a, Prkch, Camk4, Ptk2b, Pde1a, Ptpn5, Gng7, Akap11, Dusp14, Map2k1, Ppp3ca, Akap5, Pygl, Prkcg, Prkar2b, Pde8b, Ptgs2, Prkcb, Akap1
P-NP	CREB Signaling in Neurons	14 genes: Gria4, Camk2d, Pik3c3, Atf4, Adcy8, Grik1, Adcy2, Grm1, Adcy6, Gng3, Plcb4, Gng2, Rps6ka1, Camk2g	26 genes: Grm2, Camk4, Mapk1, Grm3, Gria1, Gng7, Gnb4, Camk2b, Camk2a, Adcy5, Mras, Grik2, Pik3r2, Map2k1, Grm8, Gria2, Grm4, Itpr1, Prkcg, Grm5, Grm7, Prkar2b, Prkch, Gnal, Gria3, Prkcb
P-NP	Calcium Signaling	14 genes: Tnnc1, Atp2a2, Gria4, Camk2d, Ppp3cb, Atf4, Grik1, Hdac4, Myh14, Tpm2, Trpc4, Atp2b2, Tpm4, Camk2g	21 genes: Tnnt1, Camk4, Mapk1, Atp2b1, Gria1, Tpm1, Camk2b, Camk2a, Ppp3r1, Ryr3, Ppp3ca, Casq2, Akap5, Tnnc2, Gria2, Itpr1, Prkar2b, Htr3a, Mef2c, Camkk2, Gria3
P-NP	Relaxin Signaling	12 genes: Nfkbie, Pde4a, Nfkb1, Nfkbia, Pik3c3, Adcy8, Adcy2, Adcy6, Gng3, Pde8a, Gng2, Npr2	16 genes: Mapk1, Pde1a, Gng7, Gnb4, Adcy5, Mras, Pik3r2, Map2k1, Gucy1b3, Pde2a, Gucy1a3, Pde10a, Prkar2b, Pde1b, Pde8b, Gnal
P-NP	Phospholipase C Signaling	20 genes: Nfkb1, Rhog, Ppp3cb, Gpld1, Atf4, Adcy8, Adcy2, Hdac4, Pld3, Adcy6, Ppp1r14a, Arhgef17, Rapgef3, Gng3, Rhov, Plcb4, Rhoq, Rnd3, Gng2, Fnbp1	20 genes: Fyn, Camk4, Mapk1, Rps6ka3, Gng7, Gnb4, Adcy5, Ppp3r1, Mras, Arhgef2, Map2k1, Ppp3ca, Itpr1, Prkcg, Ppp1r12b, Ppp1r12a, Mef2c, Prkch, Arhgef9, Prkcb
P-NP	Signaling by Rho Family GTPases	21 genes: Pip5k1b, Sept9, Nfkb1, Limk1, Stmn1, Rhog, Pik3c3, Gfap, Cdc42ep1, Mapk8, Rdx, Arhgef17, Gng3, Mapk12, Rhov, Rhoq, Rnd3, Gng2, Pip4k2a, Sept6, Fnbp1	20 genes: Mapk1, Ptk2b, Gng7, Ptk2, Gnb4, Ezr, Baiap2, Mras, Arhgef2, Arpc1a, Pik3r2, Map2k1, Cdc42ep3, Wasf1, Pip5k1a, Ppp1r12b, Ppp1r12a, Pard3, Arhgef9, Gnal
P-NP	Axonal Guidance Signaling	28 genes: Bmp4, Ephb2, Adam11, Limk1, Tubb3, Sema5a, Gng3, Sema6d, Gng2, Rgs3, Slit1, Pdgfa, Fzd1, Tubb2b, Ppp3cb, Igf1, Tuba8, Pik3c3, Ntrk1, Smo, Rassf5, Plcb4, Ntrk2, Sema4d, Mag, Epha5, Sema3c, Gli1	34 genes: Slit3, Mapk1, Itsn1, Ptk2, Gnb4, Ephb1, Ppp3r1, Baiap2, Mras, Arpc1a, Ablim2, Epha7, Ngef, Kalrn, Vegfc, Prkch, Gnal, Fyn, Bmp2, Epha4, Plxna2, Gng7, Wnt7a, Pik3r2, Robo2, Shank2, Map2k1, Ppp3ca, Plxnc1, Slit2, Plxnd1, Prkcg, Prkar2b, Prkcb
P-NP	Synaptic Long Term Depression	8 genes: Gria4, Lcat, Igf1, Ppm1l, Grm1, Crhr1, Plcb4, Npr2	20 genes: Grm2, Mapk1, Grm3, Gria1, Ryr3, Mras, Map2k1, Gucy1b3, Gucy1a3, Grm8, Gria2, Itpr1, Grm4, Prkcg, Grm5, Grm7, Prkch, Gnal, Prkcb, Gria3
P-NP	α-Adrenergic Signaling	7 genes: Adcy2, Adcy6, Pygb, Gng3, Pygm, Gng2, Adcy8	13 genes: Camk4, Mapk1, Pygl, Itpr1, Gng7, Prkcg, Gnb4, Prkar2b, Adcy5, Mras, Prkch, Map2k1, Prkcb
P-NP	Gap Junction Signaling	10 genes: Tubb2b, Ppp3cb, Tuba8, Pik3c3, Adcy8, Adcy2, Tubb3, Adcy6, Plcb4, Npr2	17 genes: Csnk1g1, Mapk1, Adcy5, Ppp3r1, Mras, Pik3r2, Map2k1, Ppp3ca, Gucy1b3, Htr2a, Gucy1a3, Itpr1, Drd2, Prkcg, Prkar2b, Prkch, Prkcb
P-NP	Dopamine Receptor Signaling	10 genes: Ppp1r14c, Adcy2, Adcy6, Ppp1r14a, Slc18a3, Ppm1l, Smox, Adcy8, Pcbd1, Qdpr	6 genes: Ppp1r1b, Drd2, Prkar2b, Ppp1r7, Adcy5, Ppp1r12a
P-NP	Corticotropin Releasing Hormone Signaling	10 genes: Smo, Atf4, Adcy8, Adcy2, Cnr1, Adcy6, Crhr1, Mapk12, Gli1, Npr2	13 genes: Camk4, Mapk1, Adcy5, Map2k1, Gucy1b3, Gucy1a3, Itpr1, Prkcg, Prkar2b, Mef2c, Prkch, Ptgs2, Prkcb
P-NP	Dopamine- DARPP32 Feedback in cAMP Signaling	13 genes: Kcnj16, Atp2a2, Ppp3cb, Ppm1l, Atf4, Adcy8, Ppp1r14c, Adcy2, Adcy6, Ppp1r14a, Plcb4, Kcnj5, Kcnj6	19 genes: Camk4, Csnk1g1, Kcnj4, Adcy5, Ppp1r7, Ppp3r1, Ppp3ca, Gucy1b3, Cacna1d, Gucy1a3, Ppp1r1b, Itpr1, Drd2, Prkcg, Prkar2b, Ppp1r12a, Prkch, Camkk2, Prkcb
P-NP	CXCR4 Signaling*	14 genes: Rhog, Pik3c3, Adcy8, Adcy2, Mapk8, Adcy6, Gng3, Mapk12, Plcb4, Rhov, Rhoq, Rnd3, Gng2, Fnbp1	14 genes: Mapk1, Gng7, Ptk2, Gnb4, Adcy5, Mras, Pik3r2, Map2k1, Egr1, Itpr1, Prkcg, Prkch, Gnal, Prkcb
P-NP	ILK Signaling	18 genes: Nfkb1, Ccnd1, Tgfb1i1, Rhog, Pik3c3, Ppm1l, Atf4, Itgb5, Myh14, Fermt2, Mapk8, Mapk12, Rhov, Rhoq, Rnd3, Sh2b2, Rsu1, Fnbp1	14 genes: Map2k6, Mapk1, Bmp2, Pdpk1, Ptk2, Myc, Pik3r2, Actn1, Casp3, Actn2, Vegfc, Ppp1r12a, Rps6ka5, Ptgs2
P-NP	Renin-Angiotensin Signaling*	10 genes: Adcy2, Adcy6, Mapk8, Nfkb1, Mapk12, Pik3c3, Stat1, Adcy8, Ace, Agt	13 genes: Ptk2b, Mapk1, Itpr1, Jak2, Prkcg, Ptk2, Prkar2b, Adcy5, Mras, Prkch, Pik3r2, Map2k1, Prkcb
P-NP	IL-1 Signaling	10 genes: Adcy2, Nfkbie, Mapk8, Adcy6, Gng3, Mapk12, Nfkb1, Nfkbia, Gng2, Adcy8	9 genes: Map2k6, Mapk1, Gng7, Gnb4, Prkar2b, Adcy5, Mras, Gnal, Irak2
CeA
Line-pair	Canonical Pathway	Higher gene expression	Lower gene expression
HAD1- LAD1	IL-8 Signaling	6 genes: Ccnd2, Mapk1, Mapk8, Nfkb1, Ccnd1, Tek	4 genes: Itgb2, Pik3ca, Pik3c2a, Mmp2
HAD2- LAD2	IGF-1 Signaling	7 genes: Csnk2a2, Igfbp6, Pik3ca, Jun, Pik3c2a, Stat3, Igfbp2	3 genes: Pik3c3, Mapk8, Igfbp5
HAD2- LAD2	Cardiac Hypertrophy Signaling	8 genes: Adcy9, Pik3ca, Pik3c2a, Gng13, Myl9, Jun, Eif2b1, Hspb1	6 genes: Mapk8, Eif4e, Rock2, Pik3c3, Eif2b5, Mef2c
HAD2- LAD2	Breast Cancer Regulation by Stathmin1	Adcy9, Pik3ca, Pik3c2a, Gng13, Rb1cc1, Arhgef18, Prkd3	Rock2, Camk2a, Camk2d, Pik3c3, Arhgef9
HAD2- LAD2	IL-8 Signaling	8 genes: Pik3ca, Pik3c2a, Gng13, Myl9, Jun, Vegfb, Prkd3, Itgb5	6 genes: Mapk8, Irak3, Rock2, Traf6, Pik3c3, Tek
HAD2- LAD2	Role of NFAT in Cardiac Hypertrophy	6 genes: Adcy9, Akap5, Pik3ca, Pik3c2a, Gng13, Prkd3	5 genes: Mapk8, Camk2d, Camk2a, Pik3c3, Mef2c

There were no significant canonical pathways in the AcbSh or CeA for the AA-ANA and sP-sNP line-pairs. For the AcbSh, only pathways with 15 or more genes are listed. For the CeA, only pathways with 10 or more genes are listed.

^*Indicates that similar pathways were found in the AcbSh of the HAD2-LAD2 line-pair, but are not listed because there were less than 15 genes in each pathway. There were no genes in common within these pathways between the P-NP and HAD2-LAD2 line-pairs.