KEGG   PATHWAY: cjc05031
Entry
cjc05031                    Pathway                                
Name
Amphetamine addiction - Callithrix jacchus (white-tufted-ear marmoset)
Description
Amphetamine is a psychostimulant drug that exerts persistent addictive effects. Most addictive drugs increase extracellular concentrations of dopamine (DA) in nucleus accumbens (NAc) and medial prefrontal cortex (mPFC), projection areas of mesocorticolimbic DA neurons and key components of the "brain reward circuit". Amphetamine achieves this elevation in extracellular levels of DA by promoting efflux from synaptic terminals. Acute administration of amphetamine induces phosphorylation of cAMP response element-binding protein (CREB) and expression of a number of immediate early genes (IEGs), such as c-fos. The IEGs is likely to initiate downstream molecular events, which may have important roles in the induction and maintenance of addictive states. Chronic exposure to amphetamine induces a unique transcription factor delta FosB, which plays an essential role in long-term adaptive changes in the brain.
Class
Human Diseases; Substance dependence
Pathway map
cjc05031  Amphetamine addiction
cjc05031

Other DBs
GO: 0001975
Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100393454  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
100402255  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
100395730  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
100405909  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
100403544  MAOB; amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
100407187  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
100393968  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
100406735  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X36 [KO:K04850]
100397940  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X11 [KO:K04851]
100413857  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
100411569  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X2 [KO:K05209]
100415252  GRIN2B; glutamate receptor ionotropic, NMDA 2B isoform X1 [KO:K05210]
100388195  GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X4 [KO:K05211]
100401859  GRIN2D; glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212]
100395984  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
100392161  GRIN3B; glutamate receptor ionotropic, NMDA 3B isoform X1 [KO:K05214]
100389125  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
100392029  GRIA2; glutamate receptor 2 isoform X2 [KO:K05198]
100399063  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
100398622  GRIA4; glutamate receptor 4 isoform X4 [KO:K05200]
100398535  DRD1; D(1A) dopamine receptor [KO:K04144]
100391814  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100410136  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100404028  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100399018  STX1A; syntaxin-1A isoform X1 [KO:K04560]
100397956  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X9 [KO:K04515] [EC:2.7.11.17]
100405903  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100391424  calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
100390938  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100410352  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X4 [KO:K04515] [EC:2.7.11.17]
100390180  CALM1; calmodulin-1 [KO:K02183]
100386819  CALM2; calmodulin-2 isoform X2 [KO:K02183]
100406081  CALM3; calmodulin-3 [KO:K02183]
100408289  CALML3; calmodulin-like protein 3 [KO:K02183]
100392199  CALML6; calmodulin-like protein 6 isoform X1 [KO:K02183]
100396690  CALML4; calmodulin-like protein 4 isoform X2 [KO:K02183]
108592443  CALML5; calmodulin-like protein 5 [KO:K02183]
118148021  calmodulin-1-like [KO:K02183]
100388410  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
100408515  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X2 [KO:K04632]
103787209  neuroendocrine secretory protein 55 [KO:K04632]
100412782  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100392123  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100408115  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
100407692  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
100400737  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100409206  cAMP-dependent protein kinase catalytic subunit gamma-like [KO:K04345] [EC:2.7.11.11]
118151333  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
100390614  PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
100410496  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
100396453  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100394435  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
100391612  serine/threonine-protein phosphatase PP1-gamma catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
100402258  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
100407681  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
100414156  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
100392193  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100394351  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
100408954  CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048]
100406635  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
100411140  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
100409637  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
100392579  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X6 [KO:K09047]
100411862  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
100401482  PDYN; proenkephalin-B [KO:K15840]
100387688  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
100390054  FOS; protein c-Fos [KO:K04379]
100386369  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
100387059  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100386452  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100392986  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100388148  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100400411  JUN; transcription factor Jun [KO:K04448]
100408022  FOSB; protein FosB isoform X1 [KO:K09029]
100395149  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100402327  HDAC2; LOW QUALITY PROTEIN: histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
100399690  HDAC1; histone deacetylase 1 isoform X2 [KO:K06067] [EC:3.5.1.98]
100401228  LOW QUALITY PROTEIN: histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
Compound
C00025  L-Glutamate
C00027  Hydrogen peroxide
C00076  Calcium cation
C00082  L-Tyrosine
C00355  3,4-Dihydroxy-L-phenylalanine
C00575  3',5'-Cyclic AMP
C01161  3,4-Dihydroxyphenylacetate
C01330  Sodium cation
C03758  Dopamine
D07445  Amfetamine (INN)
Reference
PMID:16724157
  Authors
Rajadhyaksha AM, Kosofsky BE
  Title
Psychostimulants, Protein phosphorylation and Gene expression: a growing role of L-type calcium channels.
  Journal
Cellscience 2:127-144 (2005)
DOI:10.1901/jaba.2005.2-127
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:16776597
  Authors
Hyman SE, Malenka RC, Nestler EJ
  Title
Neural mechanisms of addiction: the role of reward-related learning and memory.
  Journal
Annu Rev Neurosci 29:565-98 (2006)
DOI:10.1146/annurev.neuro.29.051605.113009
Reference
PMID:16151049
  Authors
Rajadhyaksha AM, Kosofsky BE
  Title
Psychostimulants, L-type calcium channels, kinases, and phosphatases.
  Journal
Neuroscientist 11:494-502 (2005)
DOI:10.1177/1073858405278236
Reference
PMID:14622123
  Authors
Dudman JT, Eaton ME, Rajadhyaksha A, Macias W, Taher M, Barczak A, Kameyama K, Huganir R, Konradi C
  Title
Dopamine D1 receptors mediate CREB phosphorylation via phosphorylation of the NMDA receptor at Ser897-NR1.
  Journal
J Neurochem 87:922-34 (2003)
DOI:10.1046/j.1471-4159.2003.02067.x
Reference
PMID:10414964
  Authors
Rajadhyaksha A, Barczak A, Macias W, Leveque JC, Lewis SE, Konradi C
  Title
L-Type Ca(2+) channels are essential for glutamate-mediated CREB phosphorylation and c-fos gene expression in striatal neurons.
  Journal
J Neurosci 19:6348-59 (1999)
DOI:10.1523/JNEUROSCI.19-15-06348.1999
Reference
PMID:8753884
  Authors
Konradi C, Leveque JC, Hyman SE
  Title
Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium.
  Journal
J Neurosci 16:4231-9 (1996)
DOI:10.1523/JNEUROSCI.16-13-04231.1996
Reference
PMID:10774721
  Authors
Berke JD, Hyman SE
  Title
Addiction, dopamine, and the molecular mechanisms of memory.
  Journal
Neuron 25:515-32 (2000)
DOI:10.1016/S0896-6273(00)81056-9
Reference
PMID:17728700
  Authors
McClung CA, Nestler EJ
  Title
Neuroplasticity mediated by altered gene expression.
  Journal
Neuropsychopharmacology 33:3-17 (2008)
DOI:10.1038/sj.npp.1301544
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
Reference
PMID:19199083
  Authors
Robertson SD, Matthies HJ, Galli A
  Title
A closer look at amphetamine-induced reverse transport and trafficking of the dopamine and norepinephrine transporters.
  Journal
Mol Neurobiol 39:73-80 (2009)
DOI:10.1007/s12035-009-8053-4
Reference
PMID:18617632
  Authors
Binda F, Dipace C, Bowton E, Robertson SD, Lute BJ, Fog JU, Zhang M, Sen N, Colbran RJ, Gnegy ME, Gether U, Javitch JA, Erreger K, Galli A
  Title
Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux.
  Journal
Mol Pharmacol 74:1101-8 (2008)
DOI:10.1124/mol.108.048447
Reference
PMID:21338876
  Authors
Sulzer D
  Title
How addictive drugs disrupt presynaptic dopamine neurotransmission.
  Journal
Neuron 69:628-49 (2011)
DOI:10.1016/j.neuron.2011.02.010
Reference
PMID:8630246
  Authors
Hyman SE
  Title
Addiction to cocaine and amphetamine.
  Journal
Neuron 16:901-4 (1996)
DOI:10.1016/S0896-6273(00)80111-7
Reference
PMID:18632938
  Authors
Renthal W, Carle TL, Maze I, Covington HE 3rd, Truong HT, Alibhai I, Kumar A, Montgomery RL, Olson EN, Nestler EJ
  Title
Delta FosB mediates epigenetic desensitization of the c-fos gene after chronic amphetamine exposure.
  Journal
J Neurosci 28:7344-9 (2008)
DOI:10.1523/JNEUROSCI.1043-08.2008
Reference
PMID:21989194
  Authors
Robison AJ, Nestler EJ
  Title
Transcriptional and epigenetic mechanisms of addiction.
  Journal
Nat Rev Neurosci 12:623-37 (2011)
DOI:10.1038/nrn3111
Reference
PMID:14529709
  Authors
Snyder GL, Galdi S, Fienberg AA, Allen P, Nairn AC, Greengard P
  Title
Regulation of AMPA receptor dephosphorylation by glutamate receptor agonists.
  Journal
Neuropharmacology 45:703-13 (2003)
DOI:10.1016/S0028-3908(03)00319-8
Reference
PMID:19222557
  Authors
Banerjee PS, Aston J, Khundakar AA, Zetterstrom TS
  Title
Differential regulation of psychostimulant-induced gene expression of brain derived neurotrophic factor and the immediate-early gene Arc in the juvenile and adult brain.
  Journal
Eur J Neurosci 29:465-76 (2009)
DOI:10.1111/j.1460-9568.2008.06601.x
Related
pathway
cjc04728  Dopaminergic synapse
KO pathway
ko05031   
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