Entry Name Amphetamine addiction - Equus przewalskii (Przewalski's horse)
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 Ortholog table Other DBs Organism Equus przewalskii (Przewalski's horse) [GN:
epz ]
Gene 103560754 voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
103563588 GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208 ]
103555146 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209 ]
103549904 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210 ]
103546604 GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211 ]
103541380 GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212 ]
103552461 GRIN3A; glutamate ionotropic receptor NMDA type subunit 3A [KO:K05213 ]
103549680 GRIA1; glutamate ionotropic receptor AMPA type subunit 1 [KO:K05197 ]
103547313 GRIA2; glutamate ionotropic receptor AMPA type subunit 2 [KO:K05198 ]
103557390 GRIA3; glutamate ionotropic receptor AMPA type subunit 3 [KO:K05199 ]
103540802 GRIA4; glutamate ionotropic receptor AMPA type subunit 4 [KO:K05200 ]
103565402 guanine nucleotide-binding protein G(s) subunit alpha [KO:K04632 ]
103550158 PPP1R1B; protein phosphatase 1 regulatory inhibitor subunit 1B [KO:K15494 ]
103566499 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
103564266 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
103555399 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
103544446 ARC; activity regulated cytoskeleton associated protein [KO:K15867 ]
103546119 activity-regulated cytoskeleton-associated protein-like [KO:K15867 ]
103548618 FOS; Fos proto-oncogene, AP-1 transcription factor subunit [KO:K04379 ]
103548960 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
103552460 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
103567008 FOSB; FosB proto-oncogene, AP-1 transcription factor subunit [KO:K09029 ]
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 LinkDB All DBs
