KEGG   PATHWAY: mfot05030
Entry
mfot05030                   Pathway                                
Name
Cocaine addiction - Microtus fortis (reed vole)
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
mfot05030  Cocaine addiction
mfot05030

Other DBs
GO: 0042220
Organism
Microtus fortis (reed vole) [GN:mfot]
Gene
126498125  tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
126500922  aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
126503460  synaptic vesicular amine transporter [KO:K08155]
126491341  chromaffin granule amine transporter isoform X1 [KO:K08155]
126512830  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
126512832  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
126503802  sodium-dependent dopamine transporter isoform X1 [KO:K05036]
126502682  D(1A) dopamine receptor [KO:K04144]
126508019  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
126508023  neuroendocrine secretory protein 55-like [KO:K04632]
126499947  metabotropic glutamate receptor 2 [KO:K04605]
126500177  metabotropic glutamate receptor 3 [KO:K04606]
126512093  guanine nucleotide-binding protein G(i) subunit alpha-3-like [KO:K04630]
126499907  guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
126500134  guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
126487932  guanine nucleotide-binding protein G(i) subunit alpha-3 isoform X1 [KO:K04630]
126510007  D(2) dopamine receptor [KO:K04145]
126512151  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
126512376  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
126512697  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
126487741  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
126509355  G-protein-signaling modulator 1 isoform X1 [KO:K15839]
126515016  regulator of G-protein signaling 9 [KO:K13765]
126508777  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
126487367  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
126515727  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
126486506  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
126489302  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
126509830  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
126489793  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
126505257  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
126509567  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
126495200  cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
126496125  proenkephalin-B [KO:K15840]
126490405  brain-derived neurotrophic factor [KO:K04355]
126497948  transcription factor Jun [KO:K04448]
126491001  protein FosB isoform X1 [KO:K09029]
126502367  nuclear factor NF-kappa-B p105 subunit [KO:K02580]
126498562  transcription factor p65 isoform X1 [KO:K04735]
126489457  cyclin-dependent kinase 5 [KO:K02090] [EC:2.7.11.22]
126492474  cyclin-dependent kinase 5 activator 1 [KO:K11716]
126509261  glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
126498437  glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
126489172  glutamate receptor ionotropic, NMDA 2B [KO:K05210]
126500346  glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
126488040  glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212]
126509906  glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
126489344  glutamate receptor ionotropic, NMDA 3B [KO:K05214]
126513894  disks large homolog 4 isoform X1 [KO:K11828]
126510543  protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
126511550  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
mfot04728  Dopaminergic synapse
KO pathway
ko05030   
LinkDB

DBGET integrated database retrieval system