KEGG   PATHWAY: bta05031
Entry
bta05031                    Pathway                                
Name
Amphetamine addiction - Bos taurus (cow)
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
bta05031  Amphetamine addiction
bta05031

Other DBs
GO: 0001975
Organism
Bos taurus (cow) [GN:bta]
Gene
280707  TH; tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
280762  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
282471  SLC18A2; synaptic vesicular amine transporter [KO:K08155]
617708  SLC18A1; chromaffin granule amine transporter [KO:K08155]
338445  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
281293  MAOA; amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
788410  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
408015  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
408013  CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
100336579  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
524212  GRIN2A; glutamate receptor ionotropic, NMDA 2A [KO:K05209]
537804  GRIN2B; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210]
535158  GRIN2C; glutamate receptor ionotropic, NMDA 2C precursor [KO:K05211]
618181  GRIN2D; glutamate receptor ionotropic, NMDA 2D [KO:K05212]
100295209  GRIN3A; glutamate receptor ionotropic, NMDA 3A precursor [KO:K05213]
616000  GRIN3B; glutamate receptor ionotropic, NMDA 3B [KO:K05214]
529618  GRIA1; glutamate receptor 1 precursor [KO:K05197]
614283  GRIA2; glutamate receptor 2 isoform 1 precursor [KO:K05198]
534626  GRIA3; glutamate receptor 3 precursor [KO:K05199]
529904  GRIA4; glutamate receptor 4 precursor [KO:K05200]
281125  DRD1; D(1A) dopamine receptor [KO:K04144]
282001  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
282325  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
282002  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
788566  STX1A; syntaxin-1A [KO:K04560]
282162  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515] [EC:2.7.11.17]
525416  CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
530719  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515] [EC:2.7.11.17]
532713  CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515] [EC:2.7.11.17]
326597  CALM; calmodulin [KO:K02183]
520277  CALM3; calmodulin-3 [KO:K02183]
617095  CALM1; calmodulin-1 [KO:K02183]
520404  CALML5; calmodulin-like protein 5 [KO:K02183]
100297344  CALM2; calmodulin-2 [KO:K02183]
617412  CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
104973792  uncharacterized protein LOC104973792 [KO:K02183]
539277  CALML4; calmodulin-like protein 4 [KO:K02183]
100337083  CAMK4; calcium/calmodulin-dependent protein kinase type IV isoform X2 [KO:K05869] [EC:2.7.11.17]
281793  GNAS; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632]
505740  ADCY5; adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
282322  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
282323  PRKACB; cAMP-dependent protein kinase catalytic subunit beta [KO:K04345] [EC:2.7.11.11]
282459  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
282318  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
516175  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
538829  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
281713  CREB1; cyclic AMP-responsive element-binding protein 1 [KO:K05870]
509827  ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450]
509107  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
281715  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
513105  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
513010  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
529566  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X5 [KO:K09048]
785086  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
534129  CREB5; cyclic AMP-responsive element-binding protein 5 [KO:K09047]
513928  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
281385  PDYN; proenkephalin-B preproprotein [KO:K15840]
519403  ARC; activity-regulated cytoskeleton-associated protein [KO:K15867]
280795  FOS; protein c-Fos [KO:K04379]
286852  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
533527  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
790867  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
282321  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
617585  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
280831  JUN; transcription factor Jun [KO:K04448]
540819  FOSB; protein FosB [KO:K09029]
613629  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
404126  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
407223  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
bta04728  Dopaminergic synapse
KO pathway
ko05031   
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