KEGG   PATHWAY: pteh05031
Entry
pteh05031                   Pathway                                
Name
Amphetamine addiction - Piliocolobus tephrosceles (Ugandan red Colobus)
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
pteh05031  Amphetamine addiction
pteh05031

Other DBs
GO: 0001975
Organism
Piliocolobus tephrosceles (Ugandan red Colobus) [GN:pteh]
Gene
111520620  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
111555708  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
111550703  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
111545765  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
111536409  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
111536420  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
111528338  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
111520328  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
111524370  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
111553102  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
111551718  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
111552106  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
111542444  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
111520094  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
111536207  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
111526784  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
111552681  GRIA1; glutamate receptor 1 [KO:K05197]
111553388  GRIA2; glutamate receptor 2 isoform X2 [KO:K05198]
111536046  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
111540088  GRIA4; glutamate receptor 4 isoform X1 [KO:K05200]
111521576  DRD1; D(1A) dopamine receptor [KO:K04144]
111542503  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
111524197  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
111530493  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
111547051  STX1A; syntaxin-1A [KO:K04560]
111552236  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
111552636  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
111537843  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
111547908  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
111550424  CALM2; calmodulin-2 [KO:K02183]
111520111  CALM3; calmodulin-3 isoform X2 [KO:K02183]
111552915  calmodulin-like [KO:K02183]
111552555  calmodulin-like [KO:K02183]
111553144  calmodulin-alpha-like [KO:K02183]
111533474  CALML6; calmodulin-like protein 6 [KO:K02183]
111554863  CALML3; calmodulin-like protein 3 [KO:K02183]
111554874  CALML5; calmodulin-like protein 5 [KO:K02183]
111538211  CALM1; calmodulin-1 [KO:K02183]
111554058  calmodulin-like [KO:K02183]
111548339  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
111549204  calmodulin-alpha-like [KO:K02183]
111527468  calmodulin-like [KO:K02183]
111540495  calmodulin [KO:K02183]
111542684  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
111555637  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoform X6 [KO:K04632]
111555638  neuroendocrine secretory protein 55 [KO:K04632]
111544335  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
111523821  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
111543418  PRKACG; cAMP-dependent protein kinase catalytic subunit gamma isoform X1 [KO:K04345] [EC:2.7.11.11]
111540404  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
111537471  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
111522255  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
111536803  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
111546019  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
111547676  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
111542753  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
111548140  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
111548991  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
111521981  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
111543707  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048]
111544982  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
111536760  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
111524755  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
111551841  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
111528965  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
111548215  PDYN; proenkephalin-B [KO:K15840]
111553380  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
111521118  FOS; proto-oncogene c-Fos [KO:K04379]
111545684  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111537850  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111547968  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
111550575  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
111536216  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
111523160  JUN; transcription factor AP-1 [KO:K04448]
111519974  FOSB; protein fosB [KO:K09029]
111537942  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
111547314  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
111547559  HDAC1; histone deacetylase 1 [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
pteh04728  Dopaminergic synapse
KO pathway
ko05031   
LinkDB

DBGET integrated database retrieval system