Entry 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 dependenceBRITE hierarchy
Pathway map Other DBs Orthology K04144 DRD1; dopamine receptor D1
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04374 ATF4, CREB2; cyclic AMP-dependent transcription factor ATF-4
K04379 FOS; proto-oncogene protein c-fos
K04448 JUN; transcription factor AP-1
K04450 ATF2, CREBP1; cyclic AMP-dependent transcription factor ATF-2
K04515 CAMK2; calcium/calmodulin-dependent protein kinase (CaM kinase) II [EC:2.7.11.17 ]
K04632 GNAS; guanine nucleotide-binding protein G(s) subunit alpha
K04850 CACNA1C, CAV1.2; voltage-dependent calcium channel L type alpha-1C
K04851 CACNA1D, CAV1.3; voltage-dependent calcium channel L type alpha-1D
K05036 SLC6A3, DAT; solute carrier family 6 (neurotransmitter transporter, dopamine) member 3
K05197 GRIA1; glutamate receptor 1
K05198 GRIA2; glutamate receptor 2
K05199 GRIA3; glutamate receptor 3
K05200 GRIA4; glutamate receptor 4
K05208 GRIN1; glutamate receptor ionotropic, NMDA 1
K05209 GRIN2A; glutamate receptor ionotropic, NMDA 2A
K05210 GRIN2B; glutamate receptor ionotropic, NMDA 2B
K05211 GRIN2C; glutamate receptor ionotropic, NMDA 2C
K05212 GRIN2D; glutamate receptor ionotropic, NMDA 2D
K05213 GRIN3A; glutamate receptor ionotropic, NMDA 3A
K05214 GRIN3B; glutamate receptor ionotropic, NMDA 3B
K05869 CAMK4; calcium/calmodulin-dependent protein kinase IV [EC:2.7.11.17 ]
K05870 CREB1; cyclic AMP-responsive element-binding protein 1
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06269 PPP1C; serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16 ]
K08155 SLC18A1_2, VMAT; MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2
K09047 CREB5, CREBPA; cyclic AMP-responsive element-binding protein 5
K09048 CREB3; cyclic AMP-responsive element-binding protein 3
K09049 ATF6B, CREBL1; cyclic AMP-dependent transcription factor ATF-6 beta
K11411 SIRT1, SIR2L1; NAD-dependent protein deacetylase sirtuin 1 [EC:2.3.1.286 ]
K15494 PPP1R1B, DARPP32; protein phosphatase 1 regulatory subunit 1B
K15840 PDYN, PENKB; proenkephalin B (prodynorphin)
K15867 ARC; activity-regulated cytoskeleton-associated protein
Compound C00355 3,4-Dihydroxy-L-phenylalanine
C01161 3,4-Dihydroxyphenylacetate
Reference Authors Rajadhyaksha AM, Kosofsky BE
Title Psychostimulants, Protein phosphorylation and Gene expression: a growing role of L-type calcium channels.
Journal Reference Authors Cunha-Oliveira T, Rego AC, Oliveira CR
Title Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs.
Journal Reference Authors Hyman SE, Malenka RC, Nestler EJ
Title Neural mechanisms of addiction: the role of reward-related learning and memory.
Journal Reference Authors Rajadhyaksha AM, Kosofsky BE
Title Psychostimulants, L-type calcium channels, kinases, and phosphatases.
Journal 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 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 Reference 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 Reference Authors Berke JD, Hyman SE
Title Addiction, dopamine, and the molecular mechanisms of memory.
Journal Reference Authors McClung CA, Nestler EJ
Title Neuroplasticity mediated by altered gene expression.
Journal Reference Authors Chao J, Nestler EJ
Title Molecular neurobiology of drug addiction.
Journal 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 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 Reference Authors Sulzer D
Title How addictive drugs disrupt presynaptic dopamine neurotransmission.
Journal Reference Authors Hyman SE
Title Addiction to cocaine and amphetamine.
Journal 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 Reference Authors Robison AJ, Nestler EJ
Title Transcriptional and epigenetic mechanisms of addiction.
Journal 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 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.
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