Entry Name Amphetamine addiction - Zalophus californianus (California sea lion)
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 Zalophus californianus (California sea lion) [GN:
zca ]
Gene 113910547 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
113911103 ARC; activity-regulated cytoskeleton-associated protein [KO:K15867 ]
113911293 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
113911484 CAMK2B; calcium/calmodulin-dependent protein kinase type II subunit beta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
113911563 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
113914325 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
113916795 CACNA1D; voltage-dependent L-type calcium channel subunit alpha-1D isoform X2 [KO:K04851 ]
113917002 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
113917422 GRIN3B; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3B [KO:K05214 ]
113918955 SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155 ]
113919173 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
113919467 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113919503 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
113921368 CAMK2G; calcium/calmodulin-dependent protein kinase type II subunit gamma isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
113921757 CACNA1C; LOW QUALITY PROTEIN: voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
113921771 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
113923011 CALML3; LOW QUALITY PROTEIN: calmodulin-like protein 3 [KO:K02183 ]
113924138 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113924414 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113925181 SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155 ]
113925843 CAMK2D; calcium/calmodulin-dependent protein kinase type II subunit delta isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
113926300 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
113929050 CAMK2A; calcium/calmodulin-dependent protein kinase type II subunit alpha isoform X1 [KO:K04515 ] [EC:2.7.11.17 ]
113933699 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
113934022 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
113934578 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
113934907 GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213 ]
113936966 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
113938980 PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494 ]
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
