KEGG   PATHWAY: gvr05031
Entry
gvr05031                    Pathway                                
Name
Amphetamine addiction - Galeopterus variegatus (Sunda flying lemur)
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
gvr05031  Amphetamine addiction
gvr05031

Other DBs
GO: 0001975
Organism
Galeopterus variegatus (Sunda flying lemur) [GN:gvr]
Gene
103595280  TH; tyrosine 3-monooxygenase isoform X1 [KO:K00501] [EC:1.14.16.2]
103588248  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
103602568  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
103600759  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
103601322  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
103601323  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
103606824  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
103595029  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850]
103603077  voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
103593496  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
103590387  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
103592420  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
103603698  GRIN2C; glutamate receptor ionotropic, NMDA 2C [KO:K05211]
103587773  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
103604523  GRIN3A; glutamate receptor ionotropic, NMDA 3A [KO:K05213]
103603494  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
103602798  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
103606746  GRIA2; glutamate receptor 2 [KO:K05198]
103591966  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
103606234  glutamate receptor 4 [KO:K05200]
103593468  DRD1; D(1A) dopamine receptor [KO:K04144]
103599847  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
103592574  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103583388  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103599669  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103596644  STX1A; syntaxin-1A [KO:K04560]
103595135  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
103583890  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
103585039  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
103592962  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
103601309  calmodulin-like protein 3 [KO:K02183]
103601310  CALML5; calmodulin-like protein 5 [KO:K02183]
103588449  CALM1; calmodulin [KO:K02183]
103601992  calmodulin-like [KO:K02183]
103591330  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
103592983  CALM3; LOW QUALITY PROTEIN: calmodulin [KO:K02183]
103599723  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
103603361  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
103608810  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
103608866  neuroendocrine secretory protein 55 [KO:K04632]
103588664  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
103589593  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
103585135  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
103591188  PPP1R1B; LOW QUALITY PROTEIN: protein phosphatase 1 regulatory subunit 1B [KO:K15494]
103582032  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
103589995  PPP1CA; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
103585436  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
103598453  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
103607967  LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-beta catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
103586701  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
103605275  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
103599295  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
103594556  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
103588716  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
103584009  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
103585217  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
103586347  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
103600172  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
103595172  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
103603638  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
103593246  PDYN; proenkephalin-B [KO:K15840]
103608738  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
103605891  FOS; proto-oncogene c-Fos [KO:K04379]
103591114  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
103598106  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103598210  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103604521  PPP3R2; calcineurin subunit B type 2 isoform X1 [KO:K06268]
103592390  JUN; transcription factor AP-1 [KO:K04448]
103594524  FOSB; protein fosB isoform X1 [KO:K09029]
103585976  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
103594928  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
103604993  HDAC2; histone deacetylase 2 [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
gvr04728  Dopaminergic synapse
KO pathway
ko05031   
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