KEGG   PATHWAY: aju05030
Entry
aju05030                    Pathway                                
Name
Cocaine addiction - Acinonyx jubatus (cheetah)
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
aju05030  Cocaine addiction
aju05030

Other DBs
GO: 0042220
Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
106971078  tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
106968187  aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
106974109  synaptic vesicular amine transporter [KO:K08155]
106971854  chromaffin granule amine transporter [KO:K08155]
106972520  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
106972743  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
106985115  sodium-dependent dopamine transporter [KO:K05036]
106975386  D(1A) dopamine receptor [KO:K04144]
106969942  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
106969924  neuroendocrine secretory protein 55 [KO:K04632]
106987051  metabotropic glutamate receptor 2 isoform X6 [KO:K04605]
106971747  metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
106977809  guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
106982494  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
106980600  D(2) dopamine receptor [KO:K04145]
106984082  adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
106973352  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
106985791  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
106989555  G-protein-signaling modulator 1 [KO:K15839]
106975338  regulator of G-protein signaling 9 isoform X1 [KO:K13765]
106967098  cyclic AMP-responsive element-binding protein 1 isoform X3 [KO:K05870]
106988085  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
106979942  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
106981255  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
106970423  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
106987262  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
106975473  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
106978069  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
106987665  cyclic AMP-responsive element-binding protein 5 isoform X6 [KO:K09047]
106983500  cyclic AMP-dependent transcription factor ATF-6 beta isoform X4 [KO:K09049]
106985991  proenkephalin-B [KO:K15840]
106970278  LOW QUALITY PROTEIN: brain-derived neurotrophic factor [KO:K04355]
106974986  transcription factor Jun [KO:K04448]
106973595  protein FosB isoform X1 [KO:K09029]
106984704  nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
106971136  transcription factor p65 [KO:K04735]
113596750  cyclin-dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
106985261  cyclin-dependent kinase 5 activator 1 [KO:K11716]
106989187  glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
106989347  glutamate receptor ionotropic, NMDA 2A [KO:K05209]
106965657  glutamate receptor ionotropic, NMDA 2B [KO:K05210]
106987730  glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
106986956  glutamate receptor ionotropic, NMDA 2D [KO:K05212]
106972048  glutamate receptor ionotropic, NMDA 3A [KO:K05213]
113596369  glutamate receptor ionotropic, NMDA 3B isoform X2 [KO:K05214]
106972413  disks large homolog 4 isoform X7 [KO:K11828]
106980464  protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
106986586  glutamate receptor 2 isoform X3 [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
aju04728  Dopaminergic synapse
KO pathway
ko05030   
LinkDB

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