Entry Name Amphetamine addiction - Pteropus vampyrus (large flying fox)
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 Organism Pteropus vampyrus (large flying fox) [GN:
pvp ]
Gene 105288852 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105288866 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X2 [KO:K04515 ] [EC:2.7.11.17 ]
105290070 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105290195 ATF2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105291624 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105293031 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105296460 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
105296533 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
105297298 CACNA1C; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
105298070 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105298404 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105298564 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
105299132 PPP1CB; serine/threonine-protein phosphatase PP1-beta catalytic subunit isoform X1 [KO:K06269 ] [EC:3.1.3.16 ]
105301307 SLC6A3; LOW QUALITY PROTEIN: sodium-dependent dopamine transporter [KO:K05036 ]
105301996 ARC; activity-regulated cytoskeleton-associated protein [KO:K15867 ]
105304363 CACNA1D; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
105305286 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105306466 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
105306745 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
105307493 PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494 ]
105309689 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
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.
Journal Related KO pathway
