KEGG   PATHWAY: shon05034
Entry
shon05034                   Pathway                                
Name
Alcoholism - Sturnira hondurensis
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
shon05034  Alcoholism
shon05034

Other DBs
GO: 0045471
Organism
Sturnira hondurensis [GN:shon]
Gene
118988339  TH; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
118983501  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
118996317  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
118975168  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
118994607  MAOB; amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
118994608  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
118998658  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
118980121  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
119002924  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
118978468  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
119000893  GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
118979746  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
118984396  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
118997724  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
119000192  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
118998487  HDAC3; histone deacetylase 3 [KO:K11404] [EC:3.5.1.98]
119002181  HDAC5; histone deacetylase 5 isoform X1 [KO:K11406] [EC:3.5.1.98]
119003120  HDAC4; histone deacetylase 4 isoform X1 [KO:K11406] [EC:3.5.1.98]
118998322  HDAC6; histone deacetylase 6 isoform X1 [KO:K11407] [EC:3.5.1.98]
118997447  HDAC7; histone deacetylase 7 isoform X1 [KO:K11408] [EC:3.5.1.98]
118994867  HDAC8; histone deacetylase 8 isoform X1 [KO:K11405] [EC:3.5.1.98]
118993771  HDAC9; histone deacetylase 9 isoform X1 [KO:K11409] [EC:3.5.1.98]
118988985  HDAC10; polyamine deacetylase HDAC10 isoform X1 [KO:K18671] [EC:3.5.1.98]
118980847  HDAC11; histone deacetylase 11 [KO:K11418] [EC:3.5.1.98]
118996215  core histone macro-H2A.1 isoform X1 [KO:K11251]
118996332  histone H2A-Bbd type 2/3-like [KO:K11251]
118996333  histone H2A-Bbd type 2/3-like [KO:K11251]
118981101  histone H2A-Bbd type 2/3-like [KO:K11251]
118981102  histone H2A-Bbd type 2/3-like [KO:K11251]
118981986  histone H2A type 2-A [KO:K11251]
118990673  histone H2A type 1 [KO:K11251]
118990676  histone H2A type 1-A-like [KO:K11251]
118990691  histone H2A type 1-like [KO:K11251]
118990694  histone H2A type 1 [KO:K11251]
118990695  histone H2A type 1 [KO:K11251]
118990696  histone H2A type 1 [KO:K11251]
118990697  histone H2A type 1-like [KO:K11251]
118990709  histone H2A type 1 [KO:K11251]
118982828  histone H2A [KO:K11251]
118975319  core histone macro-H2A.2 [KO:K11251]
118983474  histone H2A.V isoform X1 [KO:K11251]
118977898  histone H2A type 1-H-like [KO:K11251]
118977901  histone H2A type 1 [KO:K11251]
118977902  histone H2A type 1 [KO:K11251]
118977904  histone H2A type 1 [KO:K11251]
118977906  histone H2A type 1-H [KO:K11251]
119001918  histone H2AX [KO:K11251]
118978342  histone H2A.J [KO:K11251]
119002769  histone H2A type 3 [KO:K11251]
118995073  histone H2A.Z-like [KO:K11251]
118979963  histone H2A.Z [KO:K11251]
118981985  histone H2B type 2-E [KO:K11252]
118982028  histone H2B type 2-F [KO:K11252]
118990674  histone H2B type 1-A [KO:K11252]
118990675  histone H2B type 1-A [KO:K11252]
118990698  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990699  histone H2B type 1-B-like [KO:K11252]
118990700  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990701  histone H2B type 1-C/E/F/G/I-like [KO:K11252]
118990702  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990703  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990710  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990711  histone H2B type 1-C/E/F/G/I [KO:K11252]
118990720  histone H2B type 1-M-like [KO:K11252]
118982829  histone H2B [KO:K11252]
118975514  histone H2B type 2-E1 [KO:K11252]
118977426  histone H2B subacrosomal variant-like [KO:K11252]
118977897  histone H2B type 1-K [KO:K11252]
118977905  histone H2B type 1-M-like [KO:K11252]
118977907  histone H2B type 1-M [KO:K11252]
118977908  histone H2B type 1-K [KO:K11252]
118977909  histone H2B type 1-M-like [KO:K11252]
118977910  histone H2B type 1-C/E/F/G/I [KO:K11252]
118996181  histone H3.3C-like [KO:K11253]
118981556  histone H3.3A [KO:K11253]
118981932  uncharacterized protein LOC118981932 [KO:K11253]
118982027  histone H3 [KO:K11253]
118990692  histone H3.1 [KO:K11253]
118990693  histone H3.1 [KO:K11253]
118990707  histone H3.1-like [KO:K11253]
118990721  uncharacterized protein LOC118990721 [KO:K11253]
118982826  histone H3 [KO:K11253]
119000437  histone H3.3A [KO:K11253]
118977896  histone H3.1 [KO:K11253]
118977899  histone H3.1 [KO:K11253]
118977900  histone H3.1 [KO:K11253]
119003148  histone H3.3A [KO:K11253]
119003217  LOW QUALITY PROTEIN: histone H3.3C [KO:K11253]
118990704  histone H4 [KO:K11254]
118990705  histone H4 [KO:K11254]
118990706  histone H4 [KO:K11254]
118990712  histone H4 [KO:K11254]
118990713  histone H4 [KO:K11254]
118982827  histone H4 [KO:K11254]
118977911  histone H4 [KO:K11254]
118977912  histone H4 [KO:K11254]
118986237  histone H4 [KO:K11254]
118985706  HAT1; histone acetyltransferase type B catalytic subunit isoform X1 [KO:K11303] [EC:2.3.1.48]
118994966  DRD1; D(1A) dopamine receptor [KO:K04144]
118996538  guanine nucleotide-binding protein G(s) subunit alpha-like isoform X1 [KO:K04632]
118996540  neuroendocrine secretory protein 55-like [KO:K04632]
119000546  DRD2; D(2) dopamine receptor [KO:K04145]
118989455  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
118990034  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630]
119000994  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
118983964  GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534]
118998185  GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536]
118992860  GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537]
119002185  GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825]
118995666  GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538]
118992638  GNB5; guanine nucleotide-binding protein subunit beta-5 isoform X1 [KO:K04539]
118992392  GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826]
118991623  GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540]
118980656  GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541]
118997366  GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542]
119001978  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542]
118984459  GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543]
118995956  GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544]
118979604  GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545]
118980212  LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11-like [KO:K04546]
118987353  GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546]
118984142  GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 isoform X1 [KO:K04347]
118984613  GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
118978877  GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547]
118987352  GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548]
118978071  GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549]
118991774  SLC29A2; equilibrative nucleoside transporter 2 [KO:K15014]
118992101  SLC29A1; equilibrative nucleoside transporter 1 isoform X1 [KO:K15014]
118993447  SLC29A3; equilibrative nucleoside transporter 3 [KO:K15014]
119001852  ADORA2A; adenosine receptor A2a [KO:K04266]
119002796  ADORA2B; adenosine receptor A2b isoform X1 [KO:K04267]
118990736  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
118997372  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
118984085  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
118985184  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
118985682  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
119002317  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
118989103  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
118990202  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
118974492  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
118984506  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
118979891  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
118983579  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
118991453  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
118995287  CRH; corticoliberin [KO:K05256]
118983123  BDNF; brain-derived neurotrophic factor [KO:K04355]
118979587  NTRK2; BDNF/NT-3 growth factors receptor isoform X1 [KO:K04360] [EC:2.7.10.1]
118990179  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
118984370  SHC2; SHC-transforming protein 2 [KO:K17447]
118993733  SHC3; SHC-transforming protein 3 [KO:K17448]
118992600  SHC4; SHC-transforming protein 4 [KO:K17449]
119000762  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
118992372  SOS2; son of sevenless homolog 2 [KO:K03099]
119001478  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
118982230  HRAS; GTPase HRas isoform X1 [KO:K02833]
118978497  KRAS; GTPase KRas isoform X1 [KO:K07827]
118981977  NRAS; GTPase NRas [KO:K07828]
118998301  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
118989073  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
118990300  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
118992336  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
119000423  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119001903  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
118985608  PDYN; proenkephalin-B [KO:K15840]
118990028  calmodulin-1 [KO:K02183]
118998106  CALML6; calmodulin-like protein 6 [KO:K02183]
118999921  calmodulin-alpha-like [KO:K02183]
118976572  CALM1; calmodulin-1 [KO:K02183]
118992351  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
119000796  calmodulin-A-like [KO:K02183]
119000797  CALML3; calmodulin-like protein 3 [KO:K02183]
119001010  calmodulin-2/4 [KO:K02183]
119001255  CALM2; calmodulin-2 [KO:K02183]
118995942  CALM3; calmodulin-3 [KO:K02183]
118975564  CAMKK1; calcium/calmodulin-dependent protein kinase kinase 1 [KO:K00908] [EC:2.7.11.17]
118991080  CAMKK2; calcium/calmodulin-dependent protein kinase kinase 2 isoform X1 [KO:K07359] [EC:2.7.11.17]
118977337  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
118995531  FOSB; protein fosB isoform X1 [KO:K09029]
118978099  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
118991095  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
118991813  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
119001313  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
118997772  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
shon04010  MAPK signaling pathway
shon04728  Dopaminergic synapse
KO pathway
ko05034   
LinkDB

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