KEGG   PATHWAY: pvp05030
Entry
pvp05030                    Pathway                                
Name
Cocaine addiction - Pteropus vampyrus (large flying fox)
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
pvp05030  Cocaine addiction
pvp05030

Other DBs
GO: 0042220
Organism
Pteropus vampyrus (large flying fox) [GN:pvp]
Gene
105288850  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
105289063  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
105290070  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
105290195  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
105290959  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
105291491  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
105291624  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
105291735  DLG4; disks large homolog 4 isoform X3 [KO:K11828]
105291961  CDK5R1; cyclin-dependent kinase 5 activator 1 [KO:K11716]
105292202  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
105293029  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
105293217  [KO:K09047]
105293418  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
105293721  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
105294889  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
105295132  GRM2; metabotropic glutamate receptor 2 [KO:K04605]
105295155  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
105295517  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
105295663  DRD2; D(2) dopamine receptor [KO:K04145]
105296083  [KO:K04632]
105296292  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
105296460  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
105296664  SLC18A1; chromaffin granule amine transporter [KO:K08155]
105297202  GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630]
105297343  FOSB; protein fosB [KO:K09029]
105297748  RGS9; regulator of G-protein signaling 9 [KO:K13765]
105297999  RELA; transcription factor p65 [KO:K04735]
105298070  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
105298209  PDYN; proenkephalin-B [KO:K15840]
105298404  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
105298564  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
105298581  GPSM1; G-protein-signaling modulator 1 isoform X3 [KO:K15839]
105299526  TH; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
105301307  SLC6A3; LOW QUALITY PROTEIN: sodium-dependent dopamine transporter [KO:K05036]
105302266  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
105302783  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
105303436  JUN; transcription factor AP-1 [KO:K04448]
105303559  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
105303753  CDK5; cyclin-dependent-like kinase 5 isoform X1 [KO:K02090] [EC:2.7.11.22]
105304199  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
105305286  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
105305432  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
105305433  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
105306466  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
105306745  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
105307493  PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
105307882  DRD1; D(1A) dopamine receptor [KO:K04144]
105308501  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
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
pvp04728  Dopaminergic synapse
KO pathway
ko05030   

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