Table 1.
Top networks for the NAc and PrL from Ingenuity Pathway Analysis with genes differentially expressed in WT and SERT Met172 mice treated with acute and chronic cocaine
| Brain area; treatment paradigm | Network hub | N of protein‐coding genes in the network that were differentially expressed | Up‐regulated protein‐coding genes in network that reached threshold for differential expression | Down‐regulated protein‐coding genes in network that reached threshold for differential expression |
|---|---|---|---|---|
| NAc; acute | Mapk8 (JNK) | 22 | Cd24a, Cdca7, Col5A1, Dcx, Igfbpl1, Kif23, Marcksl1, Nfe2l3, Nusap1, Pbk, Prc1, Prr11, Rnasel, Rrm2, Thbs4, Top2a | Acvr1c, Cd4, Cep126, Icam1, Mme, Myoc |
| NAc; acute | Ubc (UBC) | 15 | Aspm, Fam83d, Hes6, 2810417H13Rik, Lmbr1l, Mki67, Pole, Tac2, Wdr6 | Dach1, Dgkb, Mpp7, Pde7b, S100pbp, Spock3 |
| NAc; acute | Ubc (UBC) | 13 | Ckap2l, Cpne7, Fkbp10, Grhl1, Mex3a, Olfml2b, Pbk, Rnasel, Slc26a11 | Impg1, Pld5, S100pbp, Slc35d3 |
| NAc; acute | Nfkb1; Mapk1 (NFκB; ERK) | 8 | Calb2, Sp8 | Ano3, Erdr1, Jph1, Musk, Slc22a3, Uhrf1 |
| PrL; acute | Nfkb1 (NFκB) | 29 | Cep164, Dzip1, Frem1, Luc7l3, Mcc, Mtbp, Pdcd5, Slc15a2, Tagln2 | Ano3, Bcl11b, Camk4, Dffa, Inf2, Map3k13, Nnpnt, Nvl, Pcp4l1, Pim3, Ppm1l, Slc16a3, Slc25a4, Slc25a5, Slc25a13, Smpd3, Strn, Syt2, Tmem14c, Trpc3 |
| PrL; acute | Akt1 (Akt) | 27 | Dffb, Dpysl2, Fam107a, Gng13, Hook2, Nek1, Pfdn5, Rgs11, Rpl17, Rpl37, Rpl39, Rpl22l1, Tnfrsf22/Tnfrsf23 | Adcy5, Cdc42ep3, Gnb5, Ina, Kcna1, Kcna5, Kcnab1, Lrrk2, Nefl, Nefm, Parm1, Rgs9, Ric8b, Ttll7 |
| PrL; acute | Mapk8 (JNK) | 23 | Akap8l, Arhgap31, Cbs/LOC102724560, Col5a1, Col5a3, Flnb, Psrc1, Rassf2, Tfr2, Tgfbr1 | Acvr1b, Adamts2, Add2, Cdk17, Clip4, Dach1, Igsf1, Kif11, Osbpl8, Peg10, Ppp6c, Rasd2, Spats2 |
| PrL; acute | Mapk1; Mapk3 (ERK1/2) | 22 | Akap13, C4a/C4b, Dio2, Fcgr2b, Fxyd55, Mfge8, Nktr, Wsb1, Zfp57 | Akap5, Cebpd, Chn2, Cyld, Dgkb, Dgki, Dlk1, Kcnq3, Ndfip2, Pacsin2, Sema3f, Trpc5, Wnt2 |
| PrL; acute | Mapk1 (ERK) | 22 | Arhgef5, Ccdc80, Fau, Rps25, Rps27a, Sst | Cartpt, Epha7, Got1, Irs2, Nkx6–2, Oasl2, Pcsk1, Pde10a, Pde1b, Pde1c, Pde7b, Pdyn, Penk, Rnf130, Slc5a7, Tac1 |
| NAc; chronic | Mapk1; Mapk3 (ERK1/2) | 23 | B3gnt2, Tmem158 | Abca1, Ank2, B3gnt2, Cntnap1, Irs4, Lrp1, Lrp8, Lrp1B, Ptprb, Ptprd, Ptprg, Ptprt, Ptprz1, Rasd1, Ryr2, Scn1a, Scn8a, Scube1, Slc6a11, Smg1, Tnr, Vwf |
| NAc; chronic | Nfkb1 (NFκB) | 23 | Acvrl1, Brms1, Cyp2s1, Nrgn, Peli1, Spata2l, Trim8, | Akap13, Cacna1d, Camk2d, Cyp2j6, Dscam, Epha10, Flnb, Igsf1, Lrrfip1, Myo16, Nrxn1, Rif1, Slc30a3, Slc8a1, Vsnl1, Wnt10a |
| NAc; chronic | Mapk1 (ERK) | 23 | Dlx5, Egr2, Egr3, Fosb, Homer1, Nab2, Nr4a1, Nr4a3, Pdp1, Pou3f1, Sox8, Sox10, Top2a | Adarb1, Fat1, Kcnc1, Mdn1, Mid1, Nf1, Pde1a, Prkdc, Rasgrf2, Shank1 |
| NAc; chronic | Akt1 (Akt) | 20 | Akt1s1, Arc, Dach1, Egr1, Egr4, Foxg1, Foxo1, Foxo6, Mpped2, Rxrg, Vgf | Bsn, Dzip1, Mrpl55, Nrp2, Pclo, Plxna1, Plxna4, Plxnb1, Slit2 |
| NAc; chronic | Junb (JUNB) | 18 | Junb, Klf5, Lmo2, Mme, Spry2, Tiparp | Apc, Birc6, Exph5, Faah, Hipk2, AI314180, Lpp, Macf1, Nav1, Nr2f1, Ubr4, Usp24 |
| PrL; chronic | Map2k1; Map2k2 (MAP2K1/2) | 21 | Bdnf, Btg2, Cartpt, Cck, Dusp1, Dusp6, Klf10, Nudt11, Pvalb | Adcy9, Galnt10, Gdf11, Ksr1, Mef2d, Pde10a, Plxnb2, Plxnd1, Ptprf, Ptprh, Slit1, Ssh1 |
| PrL; chronic | Mapk1; Mapk3 (ERK1/2) | 20 | Arc, Dpysl2, Il17d, Spry4, Trib1, Vapa | Aebp1, Cntnap1, Dag1, Dpysl3, Gnaz, Klhl3, Mid1, Myoc, Ndst1, Pcdhgc3, Slc12a7, Slc17a6, Trpm2, Wnk2 |
| PrL; chronic | Nfkb1 (NFκB) | 19 | 2700029M09Rik, Camk2n1, Gadd45a, Gadd45b, Gas5, Ier2, Nfil3, Pttg1, Wnt10a | C4a/C4b, Cacna1h, Cacnb1, Cacng4, Dvl3, Efs, Fosb, Peli3, Rusc2, Znf668 |
| PrL; chronic | Mapk8 (JNK) | 19 | Clk1, Cox5a, Cycs, Cyr61, Junb, Lsm1, Lsm5, Nr4a1, Snrpf, Tra2a, Zcrb1 | Arhgef10l, Cabp7, Col6a2, Ints1, Myt1l, Nlgn3, Smpd3, Ttc28 |
| PrL; chronic | Racgap1 (GTPase) | 32 | Alkbh2, C9orf40, Crk, Hjurp, Htatip2, Msrb3, Nprl2, Nrsn1, Nxf1, Ovol2 | Abca2, Adap1, Agap2, Arhgef17, Atad2, Ccnd1, Cybrd1, Evi5l, Gltscr1, Kcnd1, Lnx2, Megf8, Mex3b, Myo18a, Ncl, Nfe2l2, Pcdha2, Pcdha3, Pcdha10, Plekhg5, Rabgap1l, Srgap2 |
WT and SERT Met172 mice were treated once with 20 mg·kg−1 cocaine i.p. (acute) or on five consecutive days with 15 mg·kg−1 cocaine i.p. (chronic). Mice were killed 120 min after the last cocaine dose. Each network consists of 35 genes total. Genes within the network that were differentially expressed are listed. Network hub genes are noted in two common nomenclatures. The graphical illustration for each network can be found in the Supplementary Information. Genes with higher expression in WT than in SERT Met172 mice are up‐regulated, and molecules with lower expression in WT than in SERT Met172 mice are down‐regulated.