KEGG   PATHWAY: uah05031
Entry
uah05031                    Pathway                                
Name
Amphetamine addiction - Ursus arctos (brown bear)
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
uah05031  Amphetamine addiction
uah05031

Other DBs
GO: 0001975
Organism
Ursus arctos (brown bear) [GN:uah]
Gene
113243914  TH; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
113257543  DDC; aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
113270073  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
113251976  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
113265899  uncharacterized protein LOC113265899 [KO:K00274] [EC:1.4.3.4]
113265900  MAOB; amine oxidase [flavin-containing] B isoform X1 [KO:K00274] [EC:1.4.3.4]
113260791  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
113258052  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
113256986  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
113248424  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X3 [KO:K05208]
113270811  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
113257861  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
113244660  GRIN2C; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2C [KO:K05211]
113243350  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
113260377  GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
113242713  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
113263993  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
113255793  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
113270923  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
113260120  GRIA4; glutamate receptor 4 isoform X1 [KO:K05200]
113264115  DRD1; D(1A) dopamine receptor [KO:K04144]
113265250  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
113267584  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
113247385  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
113267789  STX1A; syntaxin-1A [KO:K04560]
113257849  CAMK2B; LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
113255589  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X3 [KO:K04515] [EC:2.7.11.17]
113259192  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X7 [KO:K04515] [EC:2.7.11.17]
113263946  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X3 [KO:K04515] [EC:2.7.11.17]
113241090  calmodulin-like [KO:K02183]
113241128  calmodulin-like protein 3 [KO:K02183]
113240902  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
113256068  calmodulin-1-like [KO:K02183]
113243394  CALM3; calmodulin-3 [KO:K02183]
113245972  CALM2; calmodulin-2 [KO:K02183]
113267365  CALM1; calmodulin-1 isoform X2 [KO:K02183]
113270682  CALML6; calmodulin-like protein 6 [KO:K02183]
113254999  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
113258768  GNAS; LOW QUALITY PROTEIN: guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632]
113258223  neuroendocrine secretory protein 55 [KO:K04632]
113252326  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
113254486  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
113247197  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
113265518  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
113244033  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
113266966  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
113240761  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
113250525  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
113250749  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
113241758  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
113264990  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
113264732  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
113245324  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
113260470  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
113242823  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X2 [KO:K09048]
113262153  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X2 [KO:K09047]
113243741  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
113258418  PDYN; proenkephalin-B [KO:K15840]
113247956  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
113270317  FOS; protein c-Fos [KO:K04379]
113270001  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
113263105  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
113259177  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X3 [KO:K04348] [EC:3.1.3.16]
113260378  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
113244743  PPP3R1; calcineurin subunit B type 1 isoform X2 [KO:K06268]
113254611  JUN; transcription factor Jun [KO:K04448]
113243427  FOSB; protein FosB isoform X1 [KO:K09029]
113259105  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
113264707  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
113268357  HDAC1; histone deacetylase 1 isoform X2 [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
uah04728  Dopaminergic synapse
KO pathway
ko05031   
LinkDB

DBGET integrated database retrieval system