KEGG   PATHWAY: ko05031Help
Entry
ko05031                     Pathway                                

Name
Amphetamine addiction
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
BRITE hierarchy
Pathway map
Amphetamine addiction
ko05031

All organismsOrtholog table
Other DBs
BSID: 
GO: 
Orthology
K00501  
tyrosine 3-monooxygenase [EC:1.14.16.2]
K01593  
aromatic-L-amino-acid decarboxylase [EC:4.1.1.28]
K08155  
MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2
K00274  
monoamine oxidase [EC:1.4.3.4]
K05036  
solute carrier family 6 (neurotransmitter transporter, dopamine) member 3
K04850  
voltage-dependent calcium channel L type alpha-1C
K04851  
voltage-dependent calcium channel L type alpha-1D
K05208  
glutamate receptor ionotropic, NMDA 1
K05209  
glutamate receptor ionotropic, NMDA 2A
K05210  
glutamate receptor ionotropic, NMDA 2B
K05211  
glutamate receptor ionotropic, NMDA 2C
K05212  
glutamate receptor ionotropic, NMDA 2D
K05213  
glutamate receptor ionotropic, NMDA 3A
K05214  
glutamate receptor ionotropic, NMDA 3B
K05197  
glutamate receptor 1
K05198  
glutamate receptor 2
K05199  
glutamate receptor 3
K05200  
glutamate receptor 4
K04144  
dopamine receptor D1
K02677  
classical protein kinase C [EC:2.7.11.13]
K04560  
syntaxin 1A
K04515  
calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17]
K02183  
calmodulin
K05869  
calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17]
K04632  
guanine nucleotide-binding protein G(s) subunit alpha
K08045  
adenylate cyclase 5 [EC:4.6.1.1]
K04345  
protein kinase A [EC:2.7.11.11]
K15494  
protein phosphatase 1 regulatory subunit 1B
K06269  
serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16]
K05870  
cyclic AMP-responsive element-binding protein 1
K04450  
cyclic AMP-dependent transcription factor ATF-2
K04374  
cyclic AMP-dependent transcription factor ATF-4
K09048  
cyclic AMP-responsive element-binding protein 3
K09047  
cyclic AMP-responsive element-binding protein 5
K09049  
cyclic AMP-dependent transcription factor ATF-6 beta
K15840  
prodynorphin
K15867  
activity-regulated cytoskeleton-associated protein
K04379  
proto-oncogene protein c-fos
K04348  
serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16]
K06268  
serine/threonine-protein phosphatase 2B regulatory subunit
K04448  
transcription factor AP-1
K09029  
protein FosB
K11411  
NAD-dependent deacetylase sirtuin 1 [EC:3.5.1.-]
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)
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)
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)
Reference
  Authors
Rajadhyaksha AM, Kosofsky BE
  Title
Psychostimulants, L-type calcium channels, kinases, and phosphatases.
  Journal
Neuroscientist 11:494-502 (2005)
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)
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)
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)
Reference
  Authors
Berke JD, Hyman SE
  Title
Addiction, dopamine, and the molecular mechanisms of memory.
  Journal
Neuron 25:515-32 (2000)
Reference
  Authors
McClung CA, Nestler EJ
  Title
Neuroplasticity mediated by altered gene expression.
  Journal
Neuropsychopharmacology 33:3-17 (2008)
Reference
  Authors
Chao J, Nestler EJ
  Title
Molecular neurobiology of drug addiction.
  Journal
Annu Rev Med 55:113-32 (2004)
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)
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)
Reference
  Authors
Sulzer D
  Title
How addictive drugs disrupt presynaptic dopamine neurotransmission.
  Journal
Neuron 69:628-49 (2011)
Reference
PMID:8630246
  Authors
Hyman SE
  Title
Addiction to cocaine and amphetamine.
  Journal
Neuron 16:901-4 (1996)
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)
Reference
  Authors
Robison AJ, Nestler EJ
  Title
Transcriptional and epigenetic mechanisms of addiction.
  Journal
Nat Rev Neurosci 12:623-37 (2011)
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)
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)

DBGET integrated database retrieval system