KEGG   PATHWAY: nle05031
Entry
nle05031                    Pathway                                
Name
Amphetamine addiction - Nomascus leucogenys (northern white-cheeked gibbon)
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
nle05031  Amphetamine addiction
nle05031

Other DBs
GO: 0001975
Organism
Nomascus leucogenys (northern white-cheeked gibbon) [GN:nle]
Gene
100591963  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
100597933  DDC; aromatic-L-amino-acid decarboxylase isoform X2 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
100586312  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
100592997  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
100589976  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
100590311  MAOB; amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
100596846  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
100580437  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
100600997  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
100607572  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
100584731  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
100594244  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
100607001  LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C [KO:K05211]
115838268  LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C-like [KO:K05211]
100589972  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
100607215  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
100600108  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
100604936  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
100587219  GRIA2; glutamate receptor 2 isoform X4 [KO:K05198]
100596839  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
100590437  GRIA4; glutamate receptor 4 isoform X3 [KO:K05200]
100582870  DRD1; D(1A) dopamine receptor [KO:K04144]
100591651  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
100590939  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
100601464  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
100582896  STX1A; syntaxin-1A [KO:K04560]
100597007  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
100600165  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
100591995  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
100580290  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X30 [KO:K04515] [EC:2.7.11.17]
100586234  calmodulin-like [KO:K02183]
100582584  CALM2; calmodulin-2 [KO:K02183]
100584686  CALML6; calmodulin-like protein 6 [KO:K02183]
100595594  CALM1; calmodulin-1 [KO:K02183]
100607765  CALML3; calmodulin-like protein 3 [KO:K02183]
100602246  CALM3; calmodulin-3 [KO:K02183]
100588287  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
100603253  CALML5; calmodulin-like protein 5 [KO:K02183]
100583900  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
101176289  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X7 [KO:K04632]
115830355  neuroendocrine secretory protein 55 [KO:K04632]
100580455  ADCY5; adenylate cyclase type 5 isoform X1 [KO:K08045] [EC:4.6.1.1]
100583577  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X8 [KO:K04345] [EC:2.7.11.11]
100579779  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100607741  PRKACG; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit gamma [KO:K04345] [EC:2.7.11.11]
100600218  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
100603005  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
100605408  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
100587142  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
100586647  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X2 [KO:K05870]
100582751  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
100588160  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
100603387  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
100595943  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
100594080  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
100597876  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
100592170  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
100600059  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
100598020  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
100593037  PDYN; proenkephalin-B [KO:K15840]
100596375  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
100585899  FOS; proto-oncogene c-Fos [KO:K04379]
100598029  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100607264  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100583664  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
100600788  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100593195  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100586501  JUN; transcription factor AP-1 [KO:K04448]
100602702  FOSB; protein fosB [KO:K09029]
100605499  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
100591684  HDAC2; histone deacetylase 2 isoform X1 [KO:K06067] [EC:3.5.1.98]
100591033  HDAC1; histone deacetylase 1 isoform X3 [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
nle04728  Dopaminergic synapse
KO pathway
ko05031   
LinkDB

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