Common pathways underlying drug addiction (WP2636)

Homo sapiens

The pathway was modeled after Figure 2 in Li, et al. 2008 and is based on the common pathways identified in their study as well as protein interaction data. Specifically, glutamate and dopamine neuroactive ligand-receptor interactions trigger long-term potentiation, MAPK and GnRH signaling and gap junction regulation (green outlined pathway nodes). Related functional modules such as depolarization, gene expression and cytoskeleton regulation are also indicated (non-outlined pathway nodes). Among the several positive feedback loops identified in this pathway, the authors highlighted fast and slow ones in red and blue, respectively. Proteins on this pathway have targeted assays available via the [ CPTAC Assay Portal]


Andra Waagmeester , Egon Willighagen , Kristina Hanspers , Alex Pico , Denise Slenter , and Eric Weitz


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Homo sapiens




Pathway Ontology

cocaine addiction pathway amphetamine addiction pathway morphine addiction pathway disease pathway drug pathway nicotine addiction pathway

Disease Ontology

alcohol dependence


Label Type Compact URI Comment
Dopamine Metabolite chemspider:661
Glutamate Metabolite wikidata:Q181136
Ca++ Metabolite chemspider:266
cAMP Metabolite chemspider:5851
DRD4 GeneProduct ensembl:ENSG00000069696
DRD1 GeneProduct ensembl:ENSG00000184845
DRD2 GeneProduct ensembl:ENSG00000149295
Gs GeneProduct ensembl:ENSG00000087460
CaM GeneProduct ensembl:ENSG00000198668
CAMK2A GeneProduct ensembl:ENSG00000070808
Inhibitor-1 GeneProduct ensembl:ENSG00000135447
PRKACG GeneProduct ensembl:ENSG00000165059
MEK1 GeneProduct ensembl:ENSG00000169032
ERK1 GeneProduct ensembl:ENSG00000102882
CREB1 GeneProduct ensembl:ENSG00000118260
CAMK4 GeneProduct ensembl:ENSG00000152495
ADCY1 GeneProduct ensembl:ENSG00000164742
Connexin 32 GeneProduct ensembl:ENSG00000169562
MEK2 GeneProduct ensembl:ENSG00000126934
ACTB GeneProduct ensembl:ENSG00000075624
ADCY1 GeneProduct ensembl:ENSG00000164742
GRIA1 GeneProduct ensembl:ENSG00000155511
GRIN1 GeneProduct ensembl:ENSG00000176884
GRM1 GeneProduct ensembl:ENSG00000152822
PRKCA GeneProduct ensembl:ENSG00000154229
Gi GeneProduct ensembl:ENSG00000127955
ERK2 GeneProduct ensembl:ENSG00000100030
ACTG1 GeneProduct ensembl:ENSG00000184009
ACTG2 GeneProduct ensembl:ENSG00000163017
ADCY8 GeneProduct ensembl:ENSG00000155897
GRIA2 GeneProduct ensembl:ENSG00000120251
GRIA3 GeneProduct ensembl:ENSG00000125675
GRIA4 GeneProduct ensembl:ENSG00000152578
GRIN2A GeneProduct ensembl:ENSG00000183454
GRM5 GeneProduct ensembl:ENSG00000168959
CAMK2A GeneProduct ensembl:ENSG00000070808
GRIN1 GeneProduct ensembl:ENSG00000176884
GRIN2A GeneProduct ensembl:ENSG00000183454
PRKCB GeneProduct ensembl:ENSG00000166501
PRKCG GeneProduct ensembl:ENSG00000126583
PRKACA GeneProduct ensembl:ENSG00000072062
PRKACB GeneProduct ensembl:ENSG00000142875
PPP1CA GeneProduct ensembl:ENSG00000172531
PPP1CB GeneProduct ensembl:ENSG00000213639
PPP1CC GeneProduct ensembl:ENSG00000186298
PRKACG GeneProduct ensembl:ENSG00000165059
PRKACA GeneProduct ensembl:ENSG00000072062
PRKACB GeneProduct ensembl:ENSG00000142875
RAF1 GeneProduct ensembl:ENSG00000132155
ARAF GeneProduct ensembl:ENSG00000078061
ARAF GeneProduct ensembl:ENSG00000078061
RAP1B GeneProduct ensembl:ENSG00000127314
RAP1A GeneProduct ensembl:ENSG00000116473


  1. Genes and (common) pathways underlying drug addiction. Li CY, Mao X, Wei L. PLoS Comput Biol. 2008 Jan;4(1):e2. PubMed Europe PMC Scholia