KEGG   PATHWAY: ptr05034Help
Entry
ptr05034                    Pathway                                

Name
Alcoholism - Pan troglodytes (chimpanzee)
Description
Alcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the rewarding effects of alcohol, dopaminergic ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) have been identified. Acute exposure to alcohol stimulates dopamine release into the NAc, which activates D1 receptors, stimulating PKA signaling and subsequent CREB-mediated gene expression,  whereas chronic alcohol exposure leads to an adaptive downregulation of this pathway, in particular of CREB function. The decreased CREB function in the NAc may promote the intake of drugs of abuse to achieve an increase in reward and thus may be involved in the regulation of positive affective states of addiction. PKA signaling also affects NMDA receptor activity and may  play an important role in neuroadaptation in response to chronic alcohol exposure.
Class
Human Diseases; Substance dependence
BRITE hierarchy
Pathway map
Alcoholism
ptr05034

All organismsOrtholog table
Other DBs
BSID: 
GO: 
Organism
Pan troglodytes (chimpanzee) [GN:ptr]
Gene
450955  
TH; tyrosine hydroxylase [KO:K00501] [EC:1.14.16.2]
463409  
DDC; dopa decarboxylase (aromatic L-amino acid decarboxylase) [KO:K01593] [EC:4.1.1.28]
464032  
SLC18A1; solute carrier family 18 (vesicular monoamine), member 1 [KO:K08155]
466213  
SLC18A2; solute carrier family 18 (vesicular monoamine), member 2 [KO:K08155]
749637  
SLC18A1; solute carrier family 18 (vesicular monoamine), member 1 [KO:K08155]
740491  
MAOA; monoamine oxidase A [KO:K00274] [EC:1.4.3.4]
465588  
MAOB; monoamine oxidase B [KO:K00274] [EC:1.4.3.4]
743285  
amine oxidase [flavin-containing] A-like; K00274 monoamine oxidase [EC:1.4.3.4] [KO:K00274] [EC:1.4.3.4]
750842  
SLC6A3; solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [KO:K05036]
465176  
GRIN1; glutamate receptor, ionotropic, N-methyl D-aspartate 1 [KO:K05208]
454396  
GRIN2A; glutamate receptor, ionotropic, N-methyl D-aspartate 2A [KO:K05209]
473373  
GRIN2B; glutamate receptor, ionotropic, N-methyl D-aspartate 2B [KO:K05210]
454868  
GRIN2C; glutamate receptor, ionotropic, N-methyl D-aspartate 2C [KO:K05211]
456180  
GRIN2D; glutamate receptor, ionotropic, N-methyl D-aspartate 2D [KO:K05212]
736408  
GRIN3A; glutamate receptor, ionotropic, N-methyl-D-aspartate 3A [KO:K05213]
GRIN3B; glutamate receptor, ionotropic, N-methyl-D-aspartate 3B [KO:K05214]
464259  
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
748850  
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
462950  
HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
738624  
HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
454721  
HDAC5; histone deacetylase 5 [KO:K11406] [EC:3.5.1.98]
460060  
HDAC4; histone deacetylase 4 [KO:K11406] [EC:3.5.1.98]
HDAC6; histone deacetylase 6 [KO:K11407] [EC:3.5.1.98]
466968  
HDAC7; histone deacetylase 7 [KO:K11408] [EC:3.5.1.98]
465712  
HDAC8; histone deacetylase 8-like [KO:K11405] [EC:3.5.1.98]
463280  
HDAC9; histone deacetylase 9 [KO:K11409] [EC:3.5.1.98]
458935  
HDAC10; histone deacetylase 10 [KO:K18671] [EC:3.5.1.98]
460190  
HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
746557  
histone H2A type 2-B-like; K11251 histone H2A [KO:K11251]
736529  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
457261  
histone H2A type 2-C-like; K11251 histone H2A [KO:K11251]
462486  
histone H2A type 1-A-like; K11251 histone H2A [KO:K11251]
469700  
HIST3H2A; histone H2A type 3-like [KO:K11251]
471887  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
465306  
H2AFX; H2A histone family, member J [KO:K11251]
471884  
histone H2A type 1-B/E-like; K11251 histone H2A [KO:K11251]
450509  
H2AFY2; H2A histone family, member Y2 [KO:K11251]
462076  
H2AFY; core histone macro-H2A.1 [KO:K11251]
747469  
histone H2A.V-like; K11251 histone H2A [KO:K11251]
464225  
histone H2A.Z-like; K11251 histone H2A [KO:K11251]
461400  
H2AFZ; H2A histone family, member Z [KO:K11251]
462490  
HIST1H2AC; histone cluster 1, H2ac [KO:K11251]
453664  
H2AFV; H2A histone family, member V [KO:K11251]
471895  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
471905  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
471909  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
748495  
histone H2A type 1-B/E-like; K11251 histone H2A [KO:K11251]
471894  
histone H2A type 1-like; K11251 histone H2A [KO:K11251]
737087  
histone H2A type 1-J-like; K11251 histone H2A [KO:K11251]
741663  
histone H2A-Bbd type 2/3-like; K11251 histone H2A [KO:K11251]
746468  
HIST2H2AA4; histone cluster 2, H2aa4 [KO:K11251]
histone H2A-Bbd type 2/3-like; K11251 histone H2A [KO:K11251]
462508  
histone H2B type 1-N-like; K11252 histone H2B [KO:K11252]
462509  
histone H2B type 1-O-like; K11252 histone H2B [KO:K11252]
463172  
histone H2B type 1-H-like; K11252 histone H2B [KO:K11252]
471869  
HIST1H2BA; histone cluster 1, H2ba [KO:K11252]
457260  
histone H2B type 2-F-like; K11252 histone H2B [KO:K11252]
748505  
histone H2B type 1-B-like; K11252 histone H2B [KO:K11252]
471880  
histone H2B type 1-C/E/F/G/I-like; K11252 histone H2B [KO:K11252]
471902  
histone H2B type 1-F/J/L-like; K11252 histone H2B [KO:K11252]
462491  
histone H2B type 1-D-like; K11252 histone H2B [KO:K11252]
462500  
HIST1H2BK; histone cluster 1, H2bk [KO:K11252]
746513  
HIST1H2BD; histone cluster 1, H2bd [KO:K11252]
462501  
HIST1H2BK; histone cluster 1, H2bk [KO:K11252]
469701  
histone H2B type 3-B-like; K11252 histone H2B [KO:K11252]
469702  
HIST1H2BB; histone cluster 1, H2bd [KO:K11252]
471883  
histone H2B type 1-C/E/F/G/I-like; K11252 histone H2B [KO:K11252]
471888  
histone H2B type 1-C/E/F/G/I-like; K11252 histone H2B [KO:K11252]
473712  
histone H2B type W-T-like; K11252 histone H2B [KO:K11252]
histone H2B type 1-C/E/F/G/I-like; K11252 histone H2B [KO:K11252]
histone H2B type 1-C/E/F/G/I-like; K11252 histone H2B [KO:K11252]
473608  
H3F3C; histone H3.3-like [KO:K11253]
738262  
H3F3B; H3 histone, family 3B (H3.3B) [KO:K11253]
737454  
HIST1H3A; histone cluster 1, H3a [KO:K11253]
462493  
histone H2A type 1-D-like; K11253 histone H3 [KO:K11253]
462506  
histone H2A type 1-like; K11253 histone H3 [KO:K11253]
463171  
histone H3.1-like; K11253 histone H3 [KO:K11253]
469476  
histone H3.2-like; K11253 histone H3 [KO:K11253]
471875  
histone H3.1-like; K11253 histone H3 [KO:K11253]
471876  
histone H3.1-like; K11253 histone H3 [KO:K11253]
471886  
histone H3.1-like; K11253 histone H3 [KO:K11253]
471907  
histone H3.1-like; K11253 histone H3 [KO:K11253]
472230  
histone H3.2-like; K11253 histone H3 [KO:K11253]
746430  
histone H3.2-like; K11253 histone H3 [KO:K11253]
histone H3.1-like; K11253 histone H3 [KO:K11253]
H3F3A; H3 histone, family 3A [KO:K11253]
462507  
histone H4-like; K11254 histone H4 [KO:K11254]
465305  
histone H4-like; K11254 histone H4 [KO:K11254]
472228  
histone H4-like; K11254 histone H4 [KO:K11254]
735611  
histone H4-like; K11254 histone H4 [KO:K11254]
736707  
histone H4-like; K11254 histone H4 [KO:K11254]
748513  
histone H4-like; K11254 histone H4 [KO:K11254]
748525  
histone H4-like; K11254 histone H4 [KO:K11254]
748532  
histone H4-like; K11254 histone H4 [KO:K11254]
748545  
histone H4-like; K11254 histone H4 [KO:K11254]
457262  
histone H4-like; K11254 histone H4 [KO:K11254]
472229  
histone H4-like protein type G-like; K11254 histone H4 [KO:K11254]
737496  
histone H4-like; K11254 histone H4 [KO:K11254]
462494  
histone H4-like; K11254 histone H4 [KO:K11254]
459737  
HAT1; histone acetyltransferase 1 [KO:K11303] [EC:2.3.1.48]
744598  
DRD1; dopamine receptor D1 [KO:K04144]
469986  
GNAS; GNAS complex locus [KO:K04632]
451553  
DRD2; dopamine receptor D2 [KO:K04145]
457093  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
472425  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
744773  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
450173  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
469458  
GNB1; guanine nucleotide binding protein (G protein), beta polypeptide 1 [KO:K04536]
739897  
GNB2; guanine nucleotide binding protein (G protein), beta polypeptide 2 [KO:K04537]
GNB3; guanine nucleotide binding protein (G protein), beta polypeptide 3 [KO:K07825]
460862  
GNB4; guanine nucleotide binding protein (G protein), beta polypeptide 4 [KO:K04538]
745402  
GNB5; guanine nucleotide binding protein (G protein), beta 5 [KO:K04539]
467457  
GNG2; guanine nucleotide binding protein (G protein), gamma 2 [KO:K07826]
740869  
GNG3; guanine nucleotide binding protein (G protein), gamma 3 [KO:K04540]
743331  
GNG4; guanine nucleotide binding protein (G protein), gamma 4 [KO:K04541]
456977  
GNG5; guanine nucleotide binding protein (G protein), gamma 5 [KO:K04542]
744391  
GNG7; guanine nucleotide binding protein (G protein), gamma 7 [KO:K04543]
uncharacterized LOC100608423; K04544 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
uncharacterized LOC100611518; K04545 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
747185  
GNG11; guanine nucleotide binding protein (G protein), gamma 11 [KO:K04546]
GNG12; guanine nucleotide binding protein (G protein), gamma 12 [KO:K04347]
468737  
guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7-like; K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
749882  
GNG13; guanine nucleotide binding protein (G protein), gamma 13 [KO:K04547]
747170  
GNGT1; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 [KO:K04548]
749133  
GNGT2; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2 [KO:K04549]
458714  
ADORA2A; adenosine A2a receptor [KO:K04266]
455009  
ADORA2B; adenosine A2b receptor [KO:K04267]
470905  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
459901  
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
739083  
ATF2; activating transcription factor 2 [KO:K04450]
ATF2; activating transcription factor 2 [KO:K04450]
744513  
ATF4; activating transcription factor 4 (tax-responsive enhancer element B67) [KO:K04374]
451704  
CREB3L1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
468672  
CREB3L3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
738928  
CREB3L2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
457341  
CREB3L4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
463318  
CREB5; cAMP responsive element binding protein 5 [KO:K09047]
745411  
ATF6B; activating transcription factor 6 beta [KO:K09049]
464215  
CRH; corticotropin releasing hormone [KO:K05256]
744617  
NPY; neuropeptide Y [KO:K05232]
503511  
BDNF; brain-derived neurotrophic factor [KO:K04355]
735394  
NTRK2; neurotrophic tyrosine kinase, receptor, type 2 [KO:K04360] [EC:2.7.10.1]
457351  
SHC1; SHC (Src homology 2 domain containing) transforming protein 1 [KO:K06279]
749831  
SHC2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
450176  
SHC3; SHC (Src homology 2 domain containing) transforming protein 3 [KO:K17448]
453414  
SHC4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
737245  
GRB2; growth factor receptor-bound protein 2 [KO:K04364]
459171  
SOS1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
452897  
SOS2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
466302  
HRAS; v-Ha-ras Harvey rat sarcoma viral oncogene homolog [KO:K02833]
473387  
KRAS; v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
742713  
NRAS; neuroblastoma RAS viral (v-ras) oncogene homolog [KO:K07828]
ARAF; v-raf murine sarcoma 3611 viral oncogene homolog [KO:K08845] [EC:2.7.11.1]
463781  
BRAF; v-raf murine sarcoma viral oncogene homolog B1 [KO:K04365] [EC:2.7.11.1]
460182  
RAF1; v-raf-1 murine leukemia viral oncogene homolog 1 [KO:K04366] [EC:2.7.11.1]
450188  
MAP2K1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
454037  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
458680  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
469860  
PDYN; prodynorphin [KO:K15840]
737566  
CALML5; calmodulin-like 5 [KO:K02183]
466008  
CALML3; calmodulin-like 3 [KO:K02183]
459213  
CALM2; calmodulin 2 (phosphorylase kinase, delta) [KO:K02183]
738819  
CALM1; calmodulin 1 (phosphorylase kinase, delta) [KO:K02183]
456153  
CALM3; calmodulin 3 (phosphorylase kinase, delta) [KO:K02183]
743250  
CALML6; calmodulin-like 6 [KO:K02183]
454438  
CAMKK1; calcium/calmodulin-dependent protein kinase kinase 1, alpha [KO:K07359] [EC:2.7.11.17]
452320  
CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2, beta [KO:K07359] [EC:2.7.11.17]
461992  
CAMK4; calcium/calmodulin-dependent protein kinase IV [KO:K05869] [EC:2.7.11.17]
744755  
PPP1R1B; protein phosphatase 1, regulatory (inhibitor) subunit 1B [KO:K15494]
462795  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isoform [KO:K06269] [EC:3.1.3.16]
745709  
PPP1CA; protein phosphatase 1, catalytic subunit, alpha isozyme [KO:K06269] [EC:3.1.3.16]
743656  
PPP1CC; protein phosphatase 1, catalytic subunit, gamma isoform [KO:K06269] [EC:3.1.3.16]
459118  
PPP1CB; protein phosphatase 1, catalytic subunit, beta isozyme [KO:K06269] [EC:3.1.3.16]
748633  
PKIA; protein kinase (cAMP-dependent, catalytic) inhibitor alpha [KO:K15985]
Compound
C00025  
L-Glutamate
C00027  
Hydrogen peroxide
C00076  
Calcium cation
C00082  
L-Tyrosine
C00212  
Adenosine
C00355  
3,4-Dihydroxy-L-phenylalanine
C00469  
Ethanol
C00575  
3',5'-Cyclic AMP
C01161  
3,4-Dihydroxyphenylacetate
C03758  
Dopamine
Reference
  Authors
Spanagel R
  Title
Alcoholism: a systems approach from molecular physiology to addictive behavior.
  Journal
Physiol Rev 89:649-705 (2009)
Reference
  Authors
Newton PM, Messing RO
  Title
Intracellular signaling pathways that regulate behavioral responses to ethanol.
  Journal
Pharmacol Ther 109:227-37 (2006)
Reference
  Authors
Mailliard WS, Diamond I
  Title
Recent advances in the neurobiology of alcoholism: the role of adenosine.
  Journal
Pharmacol Ther 101:39-46 (2004)
Reference
  Authors
Ron D, Jurd R
  Title
The "ups and downs" of signaling cascades in addiction.
  Journal
Sci STKE 2005:re14 (2005)
Reference
  Authors
Diana M, Brodie M, Muntoni A, Puddu MC, Pillolla G, Steffensen S, Spiga S, Little HJ
  Title
Enduring effects of chronic ethanol in the CNS: basis for alcoholism.
  Journal
Alcohol Clin Exp Res 27:354-61 (2003)
Reference
  Authors
Moonat S, Starkman BG, Sakharkar A, Pandey SC
  Title
Neuroscience of alcoholism: molecular and cellular mechanisms.
  Journal
Cell Mol Life Sci 67:73-88 (2010)
Reference
  Authors
Pandey SC
  Title
The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction.
  Journal
Pharmacol Ther 104:47-58 (2004)
Reference
  Authors
Zhang TA, Maldve RE, Morrisett RA
  Title
Coincident signaling in mesolimbic structures underlying alcohol reinforcement.
  Journal
Biochem Pharmacol 72:919-27 (2006)
Reference
  Authors
Maldve RE, Zhang TA, Ferrani-Kile K, Schreiber SS, Lippmann MJ, Snyder GL, Fienberg AA, Leslie SW, Gonzales RA, Morrisett RA
  Title
DARPP-32 and regulation of the ethanol sensitivity of NMDA receptors in the nucleus accumbens.
  Journal
Nat Neurosci 5:641-8 (2002)
Reference
  Authors
Lovinger DM
  Title
NMDA receptors lose their inhibitions.
  Journal
Nat Neurosci 5:614-6 (2002)
Reference
  Authors
Hyman SE, Malenka RC, Nestler EJ
  Title
Neural mechanisms of addiction: the role of reward-related learning and memory.
  Journal
Annu Rev Neurosci 29:565-98 (2006)
Reference
  Authors
Berke JD, Hyman SE
  Title
Addiction, dopamine, and the molecular mechanisms of memory.
  Journal
Neuron 25:515-32 (2000)
Reference
  Authors
Clapp P, Bhave SV, Hoffman PL
  Title
How Adaptation of the Brain to Alcohol Leads to Dependence: A Pharmacological Perspective.
  Journal
Alcohol Res Health 31:310-339 (2008)
Reference
  Authors
Jeanes ZM, Buske TR, Morrisett RA
  Title
In vivo chronic intermittent ethanol exposure reverses the polarity of synaptic plasticity in the nucleus accumbens shell.
  Journal
J Pharmacol Exp Ther 336:155-64 (2011)
Reference
  Authors
Lee AM, Messing RO
  Title
Protein kinases and addiction.
  Journal
Ann N Y Acad Sci 1141:22-57 (2008)
Reference
  Authors
Repunte-Canonigo V, Lutjens R, van der Stap LD, Sanna PP
  Title
Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.
  Journal
Brain Res 1138:48-56 (2007)
Reference
  Authors
Logrip ML, Janak PH, Ron D
  Title
Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake.
  Journal
FASEB J 22:2393-404 (2008)
Reference
  Authors
Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S
  Title
Emerging role of epigenetics in the actions of alcohol.
  Journal
Alcohol Clin Exp Res 32:1525-34 (2008)
Reference
  Authors
Pascual M, Boix J, Felipo V, Guerri C
  Title
Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in  the adult rat.
  Journal
J Neurochem 108:920-31 (2009)
Reference
  Authors
Li J, Cheng Y, Bian W, Liu X, Zhang C, Ye JH
  Title
Region-specific induction of FosB/DeltaFosB by voluntary alcohol intake: effects  of naltrexone.
  Journal
Alcohol Clin Exp Res 34:1742-50 (2010)
KO pathway
 

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