KEGG   PATHWAY: mfot05031
Entry
mfot05031                   Pathway                                
Name
Amphetamine addiction - Microtus fortis (reed vole)
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
mfot05031  Amphetamine addiction
mfot05031

Other DBs
GO: 0001975
Organism
Microtus fortis (reed vole) [GN:mfot]
Gene
126498125  tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
126500922  aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
126503460  synaptic vesicular amine transporter [KO:K08155]
126491341  chromaffin granule amine transporter isoform X1 [KO:K08155]
126512830  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
126512832  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
126503802  sodium-dependent dopamine transporter isoform X1 [KO:K05036]
126505446  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
126511130  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
126509261  glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
126498437  glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
126489172  glutamate receptor ionotropic, NMDA 2B [KO:K05210]
126500346  glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211]
126488040  glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212]
126509906  glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213]
126489344  glutamate receptor ionotropic, NMDA 3B [KO:K05214]
126510905  glutamate receptor 1 isoform X1 [KO:K05197]
126511550  glutamate receptor 2 isoform X1 [KO:K05198]
126486565  glutamate receptor 3 isoform X1 [KO:K05199]
126491718  glutamate receptor 4 isoform X1 [KO:K05200]
126502682  D(1A) dopamine receptor [KO:K04144]
126514970  protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
126502354  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
126493096  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
126492733  syntaxin-1A isoform X1 [KO:K04560]
126500968  calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515] [EC:2.7.11.17]
126501684  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
126511114  calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
126491386  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
126506775  calmodulin-like protein 3 [KO:K02183]
126506795  calmodulin-4-like isoform X1 [KO:K02183]
126507242  calmodulin-1 [KO:K02183]
126507402  calmodulin-like protein 4 isoform X1 [KO:K02183]
126494792  calmodulin-3 [KO:K02183]
126504141  calmodulin-2 [KO:K02183]
126497098  calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
126508019  guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632]
126508023  neuroendocrine secretory protein 55-like [KO:K04632]
126512151  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
126512376  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
126512697  cAMP-dependent protein kinase catalytic subunit alpha-like [KO:K04345] [EC:2.7.11.11]
126487741  cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
126510543  protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494]
126494310  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
126488330  serine/threonine-protein phosphatase PP1-alpha catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
126488640  serine/threonine-protein phosphatase PP1-alpha catalytic subunit-like [KO:K06269] [EC:3.1.3.16]
126511688  serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform X1 [KO:K06269] [EC:3.1.3.16]
126498518  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
126508777  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
126487367  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
126515727  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
126486506  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
126489302  cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048]
126509830  cyclic AMP-responsive element-binding protein 3 [KO:K09048]
126489793  cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048]
126505257  cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048]
126509567  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
126495200  cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
126496125  proenkephalin-B [KO:K15840]
126503427  activity-regulated cytoskeleton-associated protein [KO:K15867]
126515189  protein c-Fos [KO:K04379]
126491266  protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
126491367  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
126500819  calcineurin subunit B type 1 [KO:K06268]
126509907  calcineurin subunit B type 2 [KO:K06268]
126497948  transcription factor Jun [KO:K04448]
126491001  protein FosB isoform X1 [KO:K09029]
126500845  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
126499016  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
126513557  histone deacetylase 1-like [KO:K06067] [EC:3.5.1.98]
126507378  histone deacetylase 1 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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
  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
mfot04728  Dopaminergic synapse
KO pathway
ko05031   
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