KEGG   PATHWAY: psiu05034
Entry
psiu05034                   Pathway                                
Name
Alcoholism - Phocoena sinus (vaquita)
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
Pathway map
psiu05034  Alcoholism
psiu05034

Other DBs
GO: 0045471
Organism
Phocoena sinus (vaquita) [GN:psiu]
Gene
116757983  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
116759301  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
116755694  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
116741221  SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155]
116747675  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
116747892  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
116752055  SLC6A3; sodium-dependent dopamine transporter isoform X1 [KO:K05036]
116755534  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
116740277  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
116760570  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
116746356  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
116744167  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
116754946  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
116750651  GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214]
116760913  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
116763598  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
116751354  LOW QUALITY PROTEIN: histone deacetylase 2-like [KO:K06067] [EC:3.5.1.98]
116751986  HDAC3; histone deacetylase 3 isoform X1 [KO:K11404] [EC:3.5.1.98]
116756460  HDAC4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
116745565  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
116747492  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
116759991  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
116747660  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
116759049  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
116760142  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
116762829  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
116754757  histone H2A type 2-A [KO:K11251]
116754765  histone H2A type 2-A [KO:K11251]
116754796  histone H2A.Z [KO:K11251]
116761273  histone H2A.J [KO:K11251]
116762389  histone H2A type 1-H-like [KO:K11251]
116762394  histone H2A type 1-like isoform X1 [KO:K11251]
116762405  histone H2A type 1-C [KO:K11251]
116762406  histone H2A type 1-D [KO:K11251]
116762407  histone H2A type 1-like [KO:K11251]
116762408  histone H2A type 1 [KO:K11251]
116762409  histone H2A type 1-B [KO:K11251]
116762410  histone H2A type 1-B [KO:K11251]
116762411  histone H2A type 1 [KO:K11251]
116762412  histone H2A type 1-J [KO:K11251]
116762414  histone H2A type 1-H [KO:K11251]
116762447  histone H2A type 2-B [KO:K11251]
116762450  histone H2A type 2-C [KO:K11251]
116750423  histone H2A type 3 [KO:K11251]
116750637  core histone macro-H2A.1 isoform X1 [KO:K11251]
116741595  core histone macro-H2A.2 [KO:K11251]
116758731  histone H2AX [KO:K11251]
116759516  histone H2A.V isoform X1 [KO:K11251]
116747153  late histone H2B.L4-like [KO:K11252]
116754742  histone H2B type 2-F isoform X1 [KO:K11252]
116754773  histone H2B type 2-E-like [KO:K11252]
116754780  histone H2B type 2-E-like [KO:K11252]
116762190  histone H2B type 2-E-like [KO:K11252]
116762200  histone H2B type 1-A [KO:K11252]
116762246  histone H2B type 1-A-like [KO:K11252]
116762398  histone H2B type 1-L-like [KO:K11252]
116762417  histone H2B type 1-M [KO:K11252]
116762418  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
116762419  histone H2B type 1-N [KO:K11252]
116762420  histone H2B type 1-K-like [KO:K11252]
116762421  histone H2B type 1-J-like [KO:K11252]
116762422  histone H2B type 1-L-like [KO:K11252]
116762423  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
116762424  histone H2B type 1-B-like [KO:K11252]
116762425  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
116762427  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
116762428  histone H2B type 1-L [KO:K11252]
116751315  histone H2B type 3-B [KO:K11252]
116759038  histone H2B type 2-E [KO:K11252]
116759460  late histone H2B.L4 [KO:K11252]
116746429  histone H3.3A [KO:K11253]
116754945  histone H3.3A [KO:K11253]
116748062  histone H3.3A-like [KO:K11253]
116748602  histone H3.3A-like [KO:K11253]
116762381  uncharacterized protein LOC116762381 [KO:K11253]
116762401  histone H3.1 [KO:K11253]
116762402  histone H3.1 [KO:K11253]
116762403  histone H3.1 [KO:K11253]
116762441  histone H3.1-like [KO:K11253]
116762442  LOW QUALITY PROTEIN: uncharacterized protein LOC116762442 [KO:K11253]
116752127  histone H3.1 [KO:K11253]
116754753  histone H3 [KO:K11253]
116762198  uncharacterized protein LOC116762198 [KO:K11253]
116744541  histone H4-like [KO:K11254]
116760723  histone H4 [KO:K11254]
116762429  histone H4 [KO:K11254]
116762430  histone H4 [KO:K11254]
116762431  histone H4 [KO:K11254]
116762432  histone H4 [KO:K11254]
116762433  histone H4 [KO:K11254]
116762437  histone H4 [KO:K11254]
116762438  histone H4 [KO:K11254]
116756771  HAT1; histone acetyltransferase type B catalytic subunit isoform X1 [KO:K11303] [EC:2.3.1.48]
116750400  DRD1; D(1A) dopamine receptor [KO:K04144]
116740990  neuroendocrine secretory protein 55-like [KO:K04632]
116740988  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
116757987  DRD2; D(2) dopamine receptor isoform X1 [KO:K04145]
116761812  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 isoform X1 [KO:K04630]
116749946  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
116759318  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
116744142  guanine nucleotide-binding protein G(o) subunit alpha [KO:K04534]
116764574  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
116739605  GNB2; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
116760197  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
116753308  GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538]
116748817  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
116748861  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 isoform X1 [KO:K07826]
116758798  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
116742043  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
116753058  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
116763781  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
116743126  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
116752047  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
116743417  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
116744006  guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10-like [KO:K04545]
116755457  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
116759883  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 isoform X1 [KO:K04546]
116756875  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
116740969  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
116759589  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
116745853  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
116761651  SLC29A1; equilibrative nucleoside transporter 1 isoform X1 [KO:K15014]
116757850  SLC29A2; equilibrative nucleoside transporter 2 isoform X1 [KO:K15014]
116741767  SLC29A3; equilibrative nucleoside transporter 3 isoform X1 [KO:K15014]
116739170  ADORA2A; adenosine receptor A2a [KO:K04266]
116745445  ADORA2B; adenosine receptor A2b isoform X1 [KO:K04267]
116753224  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
116754197  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
116751566  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
116756730  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
116756632  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
116761029  ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374]
116755320  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
116740243  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
116758621  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
116751955  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
116759300  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
116759616  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
116762930  ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
116742639  CRH; corticoliberin [KO:K05256]
116759444  NPY; pro-neuropeptide Y isoform X1 [KO:K05232]
116758559  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
116755336  NTRK2; LOW QUALITY PROTEIN: BDNF/NT-3 growth factors receptor [KO:K04360] [EC:2.7.10.1]
116740554  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
116751918  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
116755660  SHC3; SHC-transforming protein 3 [KO:K17448]
116749591  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
116746378  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
116747062  SOS2; son of sevenless homolog 2 [KO:K03099]
116764289  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
116757893  HRAS; GTPase HRas isoform X1 [KO:K02833]
116751649  uncharacterized protein LOC116751649 [KO:K02833]
116760326  KRAS; GTPase KRas isoform X1 [KO:K07827]
116739088  NRAS; GTPase NRas [KO:K07828]
116747370  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
116759212  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
116761625  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
116747589  MAP2K1; LOW QUALITY PROTEIN: dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
116738910  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
116740620  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
116740027  PDYN; proenkephalin-B [KO:K15840]
116744236  CALM3; calmodulin-3 [KO:K02183]
116748386  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
116748713  CALM1; calmodulin-1 isoform X1 [KO:K02183]
116762110  calmodulin-1-like [KO:K02183]
116749119  calmodulin-like [KO:K02183]
116749952  calmodulin-like protein 3 [KO:K02183]
116764310  CALM2; calmodulin-2 [KO:K02183]
116745123  CAMKK1; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase kinase 1 [KO:K00908] [EC:2.7.11.17]
116738742  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
116751210  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
116744405  FOSB; protein fosB isoform X1 [KO:K09029]
116744938  PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
116739009  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
116764122  PPP1CB; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
116757793  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
116742716  PKIA; cAMP-dependent protein kinase 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
PMID:19342616
  Authors
Spanagel R
  Title
Alcoholism: a systems approach from molecular physiology to addictive behavior.
  Journal
Physiol Rev 89:649-705 (2009)
DOI:10.1152/physrev.00013.2008
Reference
PMID:16102840
  Authors
Newton PM, Messing RO
  Title
Intracellular signaling pathways that regulate behavioral responses to ethanol.
  Journal
Pharmacol Ther 109:227-37 (2006)
DOI:10.1016/j.pharmthera.2005.07.004
Reference
PMID:14729391
  Authors
Mailliard WS, Diamond I
  Title
Recent advances in the neurobiology of alcoholism: the role of adenosine.
  Journal
Pharmacol Ther 101:39-46 (2004)
DOI:10.1016/j.pharmthera.2003.10.002
Reference
PMID:16278489
  Authors
Ron D, Jurd R
  Title
The "ups and downs" of signaling cascades in addiction.
  Journal
Sci STKE 2005:re14 (2005)
DOI:10.1126/stke.3092005re14
Reference
PMID:12605085
  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)
DOI:10.1097/01.ALC.0000057121.36127.19
Reference
PMID:19756388
  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)
DOI:10.1007/s00018-009-0135-y
Reference
PMID:15500908
  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)
DOI:10.1016/j.pharmthera.2004.08.002
Reference
PMID:16764827
  Authors
Zhang TA, Maldve RE, Morrisett RA
  Title
Coincident signaling in mesolimbic structures underlying alcohol reinforcement.
  Journal
Biochem Pharmacol 72:919-27 (2006)
DOI:10.1016/j.bcp.2006.04.022
Reference
PMID:12068305
  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)
DOI:10.1038/nn877
Reference
PMID:12085089
  Authors
Lovinger DM
  Title
NMDA receptors lose their inhibitions.
  Journal
Nat Neurosci 5:614-6 (2002)
DOI:10.1038/nn0702-614
Reference
PMID:16776597
  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)
DOI:10.1146/annurev.neuro.29.051605.113009
Reference
PMID:10774721
  Authors
Berke JD, Hyman SE
  Title
Addiction, dopamine, and the molecular mechanisms of memory.
  Journal
Neuron 25:515-32 (2000)
DOI:10.1016/S0896-6273(00)81056-9
Reference
PMID:20729980
  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
PMID:20947635
  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)
DOI:10.1124/jpet.110.171009
Reference
PMID:18991950
  Authors
Lee AM, Messing RO
  Title
Protein kinases and addiction.
  Journal
Ann N Y Acad Sci 1141:22-57 (2008)
DOI:10.1196/annals.1441.022
Reference
PMID:17270154
  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)
DOI:10.1016/j.brainres.2006.09.115
Reference
PMID:18310464
  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)
DOI:10.1096/fj.07-099135
Reference
PMID:18616668
  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)
DOI:10.1111/j.1530-0277.2008.00729.x
Reference
PMID:19077056
  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)
DOI:10.1111/j.1471-4159.2008.05835.x
Reference
PMID:20626732
  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)
DOI:10.1111/j.1530-0277.2010.01261.x
Related
pathway
psiu04010  MAPK signaling pathway
psiu04728  Dopaminergic synapse
KO pathway
ko05034   
LinkDB

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