KEGG   PATHWAY: lcat05030
Entry
lcat05030                   Pathway                                
Name
Cocaine addiction - Lemur catta (Ring-tailed lemur)
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
lcat05030  Cocaine addiction
lcat05030

Other DBs
GO: 0042220
Organism
Lemur catta (Ring-tailed lemur) [GN:lcat]
Gene
123642916  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
123647351  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
123626346  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
123650462  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
123637477  amine oxidase [flavin-containing] B-like [KO:K00274] [EC:1.4.3.4]
123648852  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
123643282  LOW QUALITY PROTEIN: amine oxidase [flavin-containing] B-like [KO:K00274] [EC:1.4.3.4]
123648018  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
123623141  DRD1; D(1A) dopamine receptor [KO:K04144]
123622308  neuroendocrine secretory protein 55-like [KO:K04632]
123622310  guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632]
123623222  GRM2; metabotropic glutamate receptor 2 isoform X1 [KO:K04605]
123647779  GRM3; metabotropic glutamate receptor 3 isoform X1 [KO:K04606]
123623249  GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630]
123647150  GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630]
123635002  GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630]
123641670  DRD2; D(2) dopamine receptor isoform X1 [KO:K04145]
123630472  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
123637748  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
123635476  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
123645792  GPSM1; G-protein-signaling modulator 1 isoform X1 [KO:K15839]
123650654  RGS9; regulator of G-protein signaling 9 [KO:K13765]
123644073  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
123643408  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
123640339  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
123646158  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
123647675  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
123633885  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
123634008  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
123642645  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
123647634  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
123631772  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
123622515  PDYN; proenkephalin-B [KO:K15840]
123642542  BDNF; LOW QUALITY PROTEIN: brain-derived neurotrophic factor [KO:K04355]
123635592  JUN; transcription factor AP-1 [KO:K04448]
123623954  FOSB; protein fosB [KO:K09029]
123627206  NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580]
123641353  RELA; transcription factor p65 isoform X1 [KO:K04735]
123647514  CDK5; cyclin-dependent-like kinase 5 [KO:K02090] [EC:2.7.11.22]
123620323  CDK5R1; LOW QUALITY PROTEIN: cyclin-dependent kinase 5 activator 1 [KO:K11716]
123645581  GRIN1; glutamate receptor ionotropic, NMDA 1 [KO:K05208]
123632367  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
123639979  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
123650764  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
123623873  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
123645739  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
123632440  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
123650851  DLG4; disks large homolog 4 isoform X1 [KO:K11828]
123620832  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
123638517  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
lcat04728  Dopaminergic synapse
KO pathway
ko05030   
LinkDB

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