KEGG   PATHWAY: ray05030
Entry
ray05030                    Pathway                                
Name
Cocaine addiction - Rousettus aegyptiacus (Egyptian rousette)
Description
Drug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences.There is strong evidence that the dopaminergic system that projects from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens (NAc), and to other forebrain sites, is the major substrate of reward and reinforcement for both natural rewards and addictive drugs. Cocaine binds strongly to the dopamine-reuptake transporter, preventing the reuptake of dopamine into the nerve terminal. Because of this blocking effect, dopamine remains at high concentrations in the synapse and continues to affect adjacent neurons, producing the characteristic cocaine "high." Activated D1 receptor activates the PKA signaling pathway, and this pathway plays a critical role in mediating the behavioral responses to cocaine administration. Cocaine-induced neuroadaptations, including dopamine depletion, may underlie craving and hedonic dysregulation.
Class
Human Diseases; Substance dependence
Pathway map
ray05030  Cocaine addiction
ray05030

Other DBs
GO: 0042220
Organism
Rousettus aegyptiacus (Egyptian rousette) [GN:ray]
Gene
107513264  TH; LOW QUALITY PROTEIN: tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
107512420  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
107503755  SLC18A1; chromaffin granule amine transporter [KO:K08155]
107509743  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
107506380  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
107498765  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
107498766  amine oxidase [flavin-containing] A-like isoform X1 [KO:K00274] [EC:1.4.3.4]
107499955  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
107515942  DRD1; D(1A) dopamine receptor [KO:K04144]
107500068  neuroendocrine secretory protein 55-like [KO:K04632]
107500067  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
107504180  GRM2; metabotropic glutamate receptor 2 isoform X1 [KO:K04605]
107512461  GRM3; metabotropic glutamate receptor 3 [KO:K04606]
107516134  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
107518173  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
107513376  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
107512952  DRD2; D(2) dopamine receptor [KO:K04145]
107518038  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
107519437  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
107511590  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
107514873  GPSM1; G-protein-signaling modulator 1 isoform X1 [KO:K15839]
107510299  RGS9; regulator of G-protein signaling 9 isoform X1 [KO:K13765]
107505169  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
107504977  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
107500816  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
107509179  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
107502779  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
107511864  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
107510647  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
107499057  CREB3L2; LOW QUALITY PROTEIN: cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
107505683  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
107498439  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
107499698  PDYN; proenkephalin-B [KO:K15840]
107512170  BDNF; LOW QUALITY PROTEIN: brain-derived neurotrophic factor [KO:K04355]
107518352  JUN; transcription factor AP-1 [KO:K04448]
107516053  FOSB; protein fosB [KO:K09029]
107517900  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
107497522  RELA; transcription factor p65 [KO:K04735]
107520296  CDK5; cyclin-dependent-like kinase 5 [KO:K02090] [EC:2.7.11.22]
107514644  CDK5R1; cyclin-dependent kinase 5 activator 1 [KO:K11716]
107503090  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
107514651  GRIN2A; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2A [KO:K05209]
107508606  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
107503801  GRIN2C; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C [KO:K05211]
107498864  GRIN2D; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2D [KO:K05212]
107499583  GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
107500897  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
107509512  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
107520681  PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
107507556  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
Compound
C00025  L-Glutamate
C00027  Hydrogen peroxide
C00082  L-Tyrosine
C00355  3,4-Dihydroxy-L-phenylalanine
C00575  3',5'-Cyclic AMP
C01161  3,4-Dihydroxyphenylacetate
C03758  Dopamine
D00110  Cocaine (USP)
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:18440072
  Authors
Cunha-Oliveira T, Rego AC, Oliveira CR
  Title
Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs.
  Journal
Brain Res Rev 58:192-208 (2008)
DOI:10.1016/j.brainresrev.2008.03.002
Reference
PMID:19403004
  Authors
Chen JC, Chen PC, Chiang YC
  Title
Molecular mechanisms of psychostimulant addiction.
  Journal
Chang Gung Med J 32:148-54 (2009)
Reference
PMID:16251986
  Authors
Nestler EJ
  Title
Is there a common molecular pathway for addiction?
  Journal
Nat Neurosci 8:1445-9 (2005)
DOI:10.1038/nn1578
Reference
PMID:15091342
  Authors
Bowers MS, McFarland K, Lake RW, Peterson YK, Lapish CC, Gregory ML, Lanier SM, Kalivas PW
  Title
Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking.
  Journal
Neuron 42:269-81 (2004)
DOI:10.1016/S0896-6273(04)00159-X
Reference
PMID:12818179
  Authors
Rahman Z, Schwarz J, Gold SJ, Zachariou V, Wein MN, Choi KH, Kovoor A, Chen CK, DiLeone RJ, Schwarz SC, Selley DE, Sim-Selley LJ, Barrot M, Luedtke RR, Self D, Neve RL, Lester HA, Simon MI, Nestler EJ
  Title
RGS9 modulates dopamine signaling in the basal ganglia.
  Journal
Neuron 38:941-52 (2003)
DOI:10.1016/S0896-6273(03)00321-0
Reference
PMID:10234039
  Authors
Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR
  Title
Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor.
  Journal
J Neurosci 19:4110-22 (1999)
DOI:10.1523/JNEUROSCI.19-10-04110.1999
Reference
PMID:12064476
  Authors
Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S
  Title
Dopamine transport function is elevated in cocaine users.
  Journal
J Neurochem 81:292-300 (2002)
DOI:10.1046/j.1471-4159.2002.00820.x
Reference
PMID:14566342
  Authors
McClung CA, Nestler EJ
  Title
Regulation of gene expression and cocaine reward by CREB and DeltaFosB.
  Journal
Nat Neurosci 6:1208-15 (2003)
DOI:10.1038/nn1143
Reference
PMID:15582154
  Authors
McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ
  Title
DeltaFosB: a molecular switch for long-term adaptation in the brain.
  Journal
Brain Res Mol Brain Res 132:146-54 (2004)
DOI:10.1016/j.molbrainres.2004.05.014
Reference
PMID:11595774
  Authors
Ang E, Chen J, Zagouras P, Magna H, Holland J, Schaeffer E, Nestler EJ
  Title
Induction of nuclear factor-kappaB in nucleus accumbens by chronic cocaine administration.
  Journal
J Neurochem 79:221-4 (2001)
DOI:10.1046/j.1471-4159.2001.00563.x
Reference
PMID:11268215
  Authors
Bibb JA, Chen J, Taylor JR, Svenningsson P, Nishi A, Snyder GL, Yan Z, Sagawa ZK, Ouimet CC, Nairn AC, Nestler EJ, Greengard P
  Title
Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5.
  Journal
Nature 410:376-80 (2001)
DOI:10.1038/35066591
Reference
PMID:14746512
  Authors
Chao J, Nestler EJ
  Title
Molecular neurobiology of drug addiction.
  Journal
Annu Rev Med 55:113-32 (2004)
DOI:10.1146/annurev.med.55.091902.103730
Related
pathway
ray04728  Dopaminergic synapse
KO pathway
ko05030   
LinkDB

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