KEGG   PATHWAY: clud05030
Entry
clud05030                   Pathway                                
Name
Cocaine addiction - Canis lupus dingo (dingo)
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
clud05030  Cocaine addiction
clud05030

Other DBs
GO: 0042220
Organism
Canis lupus dingo (dingo) [GN:clud]
Gene
112663223  TH; LOW QUALITY PROTEIN: tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
112661383  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
112669792  SLC18A1; chromaffin granule amine transporter [KO:K08155]
112672396  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
112673161  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
112673162  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
112662644  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
112651600  DRD1; D(1A) dopamine receptor [KO:K04144]
112674185  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
112674186  neuroendocrine secretory protein 55 [KO:K04632]
112665856  GRM2; metabotropic glutamate receptor 2 isoform X1 [KO:K04605]
112675004  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
112661326  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
112640707  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630]
112665815  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
112671319  DRD2; D(2) dopamine receptor isoform X1 [KO:K04145]
112677166  ADCY5; adenylate cyclase type 5 isoform X2 [KO:K08045] [EC:4.6.1.1]
112666620  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
112640987  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
112677436  GPSM1; G-protein-signaling modulator 1 isoform X1 [KO:K15839]
112652942  RGS9; LOW QUALITY PROTEIN: regulator of G-protein signaling 9 [KO:K13765]
112656471  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
112668134  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
112667576  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
112647736  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
112670436  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
112650165  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
112663293  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
112666968  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
112670641  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
112641337  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
112673702  PDYN; proenkephalin-B [KO:K15840]
112667789  BDNF; brain-derived neurotrophic factor isoform X1 [KO:K04355]
112647115  JUN; transcription factor Jun [KO:K04448]
112645298  FOSB; protein FosB isoform X1 [KO:K09029]
112644595  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X3 [KO:K02580]
112659193  RELA; transcription factor p65 isoform X1 [KO:K04735]
112663900  CDK5; cyclin-dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
112655150  CDK5R1; cyclin-dependent kinase 5 activator 1 [KO:K11716]
112677485  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
112640386  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
112665422  GRIN2B; glutamate receptor ionotropic, NMDA 2B isoform X1 [KO:K05210]
112672773  GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
112645204  GRIN2D; glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212]
112650030  GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
112666165  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
112647484  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
112655190  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
112654419  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
clud04728  Dopaminergic synapse
KO pathway
ko05030   
LinkDB

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