KEGG   PATHWAY: eju05031
Entry
eju05031                    Pathway                                
Name
Amphetamine addiction - Eumetopias jubatus (Steller sea lion)
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
eju05031  Amphetamine addiction
eju05031

Other DBs
GO: 0001975
Organism
Eumetopias jubatus (Steller sea lion) [GN:eju]
Gene
114220499  TH; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
114213688  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
114200801  SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155]
114223104  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
114216818  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
114216876  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
114198569  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
114222521  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
114225091  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
114201744  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
114219938  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
114221701  GRIN2B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2B [KO:K05210]
114216269  GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
114197198  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
114213551  GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
114226323  GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214]
114211884  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
114210193  GRIA2; glutamate receptor 2 isoform X1 [KO:K05198]
114223722  GRIA3; glutamate receptor 3 [KO:K05199]
114211227  GRIA4; glutamate receptor 4 [KO:K05200]
114208554  DRD1; D(1A) dopamine receptor [KO:K04144]
114196710  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
114202995  protein kinase C alpha type-like [KO:K19662] [EC:2.7.11.13]
114202996  protein kinase C alpha type-like [KO:K19662] [EC:2.7.11.13]
114198767  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
114201798  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
114214428  STX1A; syntaxin-1A [KO:K04560]
114202281  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
114211871  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
114211898  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
114214078  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
114222643  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
114209406  calmodulin-like [KO:K02183]
114209774  CALM2; calmodulin-2 [KO:K02183]
114217752  calmodulin-like [KO:K02183]
114217770  LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183]
114218775  calmodulin-like [KO:K02183]
114213217  CALML6; calmodulin-like protein 6 [KO:K02183]
114197096  CALM3; calmodulin-3 [KO:K02183]
114197118  calmodulin-like [KO:K02183]
114204978  CALM1; calmodulin-1 [KO:K02183]
114206437  CALML4; calmodulin-like protein 4 isoform X1 [KO:K02183]
114208735  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X1 [KO:K05869] [EC:2.7.11.17]
114197913  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
114197962  neuroendocrine secretory protein 55 [KO:K04632]
114199416  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
114208397  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
114197723  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
114198484  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
114219135  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
114220523  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
114205825  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
114215964  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
114224124  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
114218458  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
114218277  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
114226347  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
114211711  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
114198708  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
114215177  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
114221152  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
114203954  cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
114203955  cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
114222060  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
114220606  PDYN; proenkephalin-B [KO:K15840]
114202692  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
114207358  FOS; proto-oncogene c-Fos [KO:K04379]
114217489  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114201320  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114214123  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
114218910  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
114213552  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
114212152  JUN; transcription factor AP-1 [KO:K04448]
114197211  FOSB; protein fosB isoform X1 [KO:K09029]
114214155  SIRT1; NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
114216997  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
114209980  HDAC2; histone deacetylase 2 isoform X1 [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
eju04728  Dopaminergic synapse
KO pathway
ko05031   
LinkDB

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