KEGG   PATHWAY: lruf05031
Entry
lruf05031                   Pathway                                
Name
Amphetamine addiction - Lynx rufus (bobcat)
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
lruf05031  Amphetamine addiction
lruf05031

Other DBs
GO: 0001975
Organism
Lynx rufus (bobcat) [GN:lruf]
Gene
124527888  tyrosine 3-monooxygenase [KO:K00501] [EC:1.14.16.2]
124524463  aromatic-L-amino-acid decarboxylase isoform X1 [KO:K01593] [EC:4.1.1.28 4.1.1.105]
124520994  chromaffin granule amine transporter-like isoform X1 [KO:K08155]
124507164  synaptic vesicular amine transporter [KO:K08155]
124509467  amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
124509695  amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
124510500  sodium-dependent dopamine transporter [KO:K05036]
124501399  voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
124522821  voltage-dependent L-type calcium channel subunit alpha-1D isoform X1 [KO:K04851]
124522398  glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208]
124517962  glutamate receptor ionotropic, NMDA 2A [KO:K05209]
124502547  glutamate receptor ionotropic, NMDA 2B [KO:K05210]
124513155  glutamate receptor ionotropic, NMDA 2C [KO:K05211]
124510950  glutamate receptor ionotropic, NMDA 2D [KO:K05212]
124502492  glutamate receptor ionotropic, NMDA 3A [KO:K05213]
124527681  LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B-like [KO:K05214]
124507151  glutamate receptor 1 isoform X1 [KO:K05197]
124520524  glutamate receptor 2 isoform X1 [KO:K05198]
124513900  glutamate receptor 3 [KO:K05199]
124505206  glutamate receptor 4 isoform X1 [KO:K05200]
124506839  D(1A) dopamine receptor [KO:K04144]
124513500  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
124517730  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
124527789  protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
124519367  syntaxin-1A [KO:K04560]
124524655  calcium/calmodulin-dependent protein kinase type II subunit beta [KO:K04515] [EC:2.7.11.17]
124520612  calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515] [EC:2.7.11.17]
124506916  calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515] [EC:2.7.11.17]
124521364  calcium/calmodulin-dependent protein kinase type II subunit alpha-like [KO:K04515] [EC:2.7.11.17]
124503379  calmodulin-1 [KO:K02183]
124510996  calmodulin-1 [KO:K02183]
124512578  calmodulin-1 [KO:K02183]
124514424  LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183]
124508455  LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
124502502  calmodulin-like protein 3 [KO:K02183]
124502628  calmodulin-like [KO:K02183]
124519754  calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
124503012  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
124503255  neuroendocrine secretory protein 55 [KO:K04632]
124526579  adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
124514583  cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
124524048  cAMP-dependent protein kinase catalytic subunit alpha isoform X1 [KO:K04345] [EC:2.7.11.11]
124513137  protein phosphatase 1 regulatory subunit 1B [KO:K15494]
124518235  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
124504709  serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269] [EC:3.1.3.16]
124502925  serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
124516566  cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
124514138  cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
124502100  cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
124524408  cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
124506275  cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048]
124521809  cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
124501745  cyclic AMP-responsive element-binding protein 3-like isoform X1 [KO:K09048]
124523866  cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
124524308  cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
124528650  cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049]
124503154  proenkephalin-B-like [KO:K15840]
124507494  LOW QUALITY PROTEIN: activity-regulated cytoskeleton-associated protein-like [KO:K15867]
124512631  protein c-Fos [KO:K04379]
124519949  serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
124521006  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124506908  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
124504103  calcineurin subunit B type 1 [KO:K06268]
124502506  calcineurin subunit B type 2 [KO:K06268]
124516273  transcription factor Jun [KO:K04448]
124511021  protein FosB [KO:K09029]
124506847  NAD-dependent protein deacetylase sirtuin-1 isoform X1 [KO:K11411] [EC:2.3.1.286]
124528271  histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
124514885  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
lruf04728  Dopaminergic synapse
KO pathway
ko05031   
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