| Entry |
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| Name |
Amphetamine addiction
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| 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.
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| Class |
Human Diseases; Substance dependence
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| Pathway map |

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| Other DBs |
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| Orthology |
| | | aromatic-L-amino-acid decarboxylase [EC: 4.1.1.28] | | MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2 | | | | solute carrier family 6 (neurotransmitter transporter, dopamine) member 3 | | voltage-dependent calcium channel L type alpha-1C | | voltage-dependent calcium channel L type alpha-1D | | glutamate receptor ionotropic, NMDA 1 | | glutamate receptor ionotropic, NMDA 2A | | glutamate receptor ionotropic, NMDA 2B | | glutamate receptor ionotropic, NMDA 2C | | glutamate receptor ionotropic, NMDA 2D | | glutamate receptor ionotropic, NMDA 3A | | glutamate receptor ionotropic, NMDA 3B | | glutamate receptor 1 | | glutamate receptor 2 | | glutamate receptor 3 | | glutamate receptor 4 | | dopamine receptor D1 | | | | syntaxin 1A | | calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC: 2.7.11.17] | | calmodulin | | calcium/calmodulin-dependent protein kinase IV [EC: 2.7.11.17] | | guanine nucleotide-binding protein G(s) subunit alpha | | | | | | protein phosphatase 1 regulatory subunit 1B | | protein phosphatase 1, catalytic subunit [EC: 3.1.3.16] | | cyclic AMP-responsive element-binding protein 1 | | cyclic AMP-dependent transcription factor ATF-2 | | cyclic AMP-dependent transcription factor ATF-4 | | cyclic AMP-responsive element-binding protein 3 | | cyclic AMP-responsive element-binding protein 5 | | cyclic AMP-dependent transcription factor ATF-6 beta | | prodynorphin | | activity-regulated cytoskeleton-associated protein | | proto-oncogene protein c-fos | | protein phosphatase 3, catalytic subunit [EC: 3.1.3.16] | | protein phosphatase 3, regulatory subunit | | transcription factor AP-1 | | protein FosB | | NAD-dependent deacetylase sirtuin 1 [EC:3.5.1.-] |
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| Compound |
| L-Glutamate | | Hydrogen peroxide | | Calcium cation | | L-Tyrosine | | 3,4-Dihydroxy-L-phenylalanine | | 3',5'-Cyclic AMP | | 3,4-Dihydroxyphenylacetate | | Sodium cation | | Dopamine | | Amfetamine (INN) |
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| Reference |
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| Title |
Psychostimulants, Protein phosphorylation and Gene expression: a growing role of L-type calcium channels. |
| Journal |
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| Reference |
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| Title |
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| Journal |
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| Authors |
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| Title |
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| Journal |
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| Title |
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| Journal |
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| Title |
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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 |
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| Title |
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Annu Rev Med 55:113-32 (2004) |
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| Title |
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| Journal |
Mol Neurobiol 39:73-80 (2009) |
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| Title |
Syntaxin 1A interaction with the dopamine transporter promotes amphetamine-induced dopamine efflux. |
| Journal |
Mol Pharmacol 74:1101-8 (2008) |
| Reference |
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| Authors |
Sulzer D |
| Title |
How addictive drugs disrupt presynaptic dopamine neurotransmission. |
| Journal |
Neuron 69:628-49 (2011) |
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| Authors |
Hyman SE |
| Title |
Addiction to cocaine and amphetamine. |
| Journal |
Neuron 16:901-4 (1996) |
| Reference |
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| 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 |
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| Authors |
Robison AJ, Nestler EJ |
| Title |
Transcriptional and epigenetic mechanisms of addiction. |
| Journal |
Nat Rev Neurosci 12:623-37 (2011) |
| Reference |
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| 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 |
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| 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) |