KEGG   PATHWAY: mlf05031
Entry
mlf05031                    Pathway                                
Name
Amphetamine addiction - Myotis lucifugus (little brown bat)
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
mlf05031  Amphetamine addiction
mlf05031

Other DBs
GO: 0001975
Organism
Myotis lucifugus (little brown bat) [GN:mlf]
Gene
102441909  DDC; aromatic-L-amino-acid decarboxylase [KO:K01593] [EC:4.1.1.28 4.1.1.105]
102438995  SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155]
102438871  SLC18A1; chromaffin granule amine transporter [KO:K08155]
102429402  MAOA; LOW QUALITY PROTEIN: amine oxidase [flavin-containing] A [KO:K00274] [EC:1.4.3.4]
102429703  MAOB; amine oxidase [flavin-containing] B [KO:K00274] [EC:1.4.3.4]
102424965  SLC6A3; sodium-dependent dopamine transporter [KO:K05036]
102424719  CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C isoform X1 [KO:K04850]
102420982  CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851]
102436175  GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209]
102433108  GRIN2B; glutamate receptor ionotropic, NMDA 2B [KO:K05210]
102430817  GRIN3A; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3A [KO:K05213]
102425604  GRIN3B; glutamate receptor ionotropic, NMDA 3B isoform X1 [KO:K05214]
102421761  GRIA1; glutamate receptor 1 isoform X1 [KO:K05197]
102441353  GRIA2; glutamate receptor 2 isoform X3 [KO:K05198]
102438664  GRIA3; glutamate receptor 3 isoform X1 [KO:K05199]
102426637  GRIA4; glutamate receptor 4 isoform X1 [KO:K05200]
102427259  DRD1; D(1A) dopamine receptor [KO:K04144]
102438932  PRKCA; protein kinase C alpha type isoform X2 [KO:K02677] [EC:2.7.11.13]
102428240  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
102419083  protein kinase C gamma type-like [KO:K19663] [EC:2.7.11.13]
102433557  STX1A; syntaxin-1A [KO:K04560]
102428043  LOW QUALITY PROTEIN: calcium/calmodulin-dependent protein kinase type II subunit delta-like [KO:K04515] [EC:2.7.11.17]
102427134  CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X5 [KO:K04515] [EC:2.7.11.17]
102440347  CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515] [EC:2.7.11.17]
102430787  CALM2; calmodulin-2 isoform X1 [KO:K02183]
102417912  calmodulin-A-like isoform X1 [KO:K02183]
102419493  calmodulin-like protein 3 [KO:K02183]
102419808  calmodulin-like protein 5 [KO:K02183]
102426645  CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183]
102434863  CALM1; calmodulin-1 [KO:K02183]
102440407  calmodulin-like [KO:K02183]
102443136  calmodulin-like [KO:K02183]
102433506  CAMK4; calcium/calmodulin-dependent protein kinase type IV [KO:K05869] [EC:2.7.11.17]
102428502  GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X11 [KO:K04632]
102433989  neuroendocrine secretory protein 55-like [KO:K04632]
102425254  ADCY5; LOW QUALITY PROTEIN: adenylate cyclase type 5 [KO:K08045] [EC:4.6.1.1]
102437773  PRKACB; cAMP-dependent protein kinase catalytic subunit beta isoform X1 [KO:K04345] [EC:2.7.11.11]
102417960  PRKACA; LOW QUALITY PROTEIN: cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
102437833  PPP1R1B; protein phosphatase 1 regulatory subunit 1B [KO:K15494]
102437203  PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269] [EC:3.1.3.16]
102436383  serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102429857  PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X2 [KO:K06269] [EC:3.1.3.16]
102417633  PPP1CC; serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269] [EC:3.1.3.16]
102428529  CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870]
102418405  ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450]
102429560  ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374]
102431250  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048]
102416978  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048]
102443216  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048]
102427186  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
102421849  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048]
102439961  CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047]
102428756  ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049]
102431576  PDYN; proenkephalin-B [KO:K15840]
102417433  FOS; proto-oncogene c-Fos [KO:K04379]
102434410  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102441003  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102421207  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
102430192  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
102428803  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
102437415  JUN; LOW QUALITY PROTEIN: transcription factor AP-1 [KO:K04448]
102428458  FOSB; protein fosB [KO:K09029]
102421566  SIRT1; NAD-dependent protein deacetylase sirtuin-1 [KO:K11411] [EC:2.3.1.286]
102428494  HDAC1; histone deacetylase 1 isoform X1 [KO:K06067] [EC:3.5.1.98]
102425617  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
mlf04728  Dopaminergic synapse
KO pathway
ko05031   
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