Entry
Name
Amphetamine addiction - Rattus norvegicus (rat)
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 dependence
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Rattus norvegicus (rat) [GN:
rno ]
Gene
25549 Slc18a2; synaptic vesicular amine transporter [KO:K08155 ]
25693 Slc18a1; chromaffin granule amine transporter [KO:K08155 ]
24898 Slc6a3; sodium-dependent dopamine transporter [KO:K05036 ]
24239 Cacna1c; voltage-dependent L-type calcium channel subunit alpha-1C [KO:K04850 ]
29716 Cacna1d; voltage-dependent L-type calcium channel subunit alpha-1D [KO:K04851 ]
24408 Grin1; glutamate receptor ionotropic, NMDA 1 isoform 1a precursor [KO:K05208 ]
24409 Grin2a; glutamate receptor ionotropic, NMDA 2A precursor [KO:K05209 ]
24410 Grin2b; glutamate receptor ionotropic, NMDA 2B precursor [KO:K05210 ]
24411 Grin2c; glutamate receptor ionotropic, NMDA 2C [KO:K05211 ]
24412 Grin2d; glutamate receptor ionotropic, NMDA 2D precursor [KO:K05212 ]
191573 Grin3a; glutamate receptor ionotropic, NMDA 3A isoform 1 precursor [KO:K05213 ]
170796 Grin3b; glutamate receptor ionotropic, NMDA 3B precursor [KO:K05214 ]
50592 Gria1; glutamate receptor 1 precursor [KO:K05197 ]
29627 Gria2; glutamate receptor 2 isoform 2 precursor [KO:K05198 ]
29628 Gria3; glutamate receptor 3 isoform 2 precursor [KO:K05199 ]
29629 Gria4; glutamate receptor 4 isoform 2 precursor [KO:K05200 ]
25400 Camk2a; calcium/calmodulin-dependent protein kinase type II subunit alpha [KO:K04515 ] [EC:2.7.11.17 ]
24246 Camk2d; calcium/calmodulin-dependent protein kinase type II subunit delta [KO:K04515 ] [EC:2.7.11.17 ]
24245 Camk2b; calcium/calmodulin-dependent protein kinase type II subunit beta isoform 2 [KO:K04515 ] [EC:2.7.11.17 ]
171140 Camk2g; calcium/calmodulin-dependent protein kinase type II subunit gamma [KO:K04515 ] [EC:2.7.11.17 ]
24896 Gnas; SCG6 (secretogranin VI) isoform SCG6 precursor [KO:K04632 ]
360616 Ppp1r1b; protein phosphatase 1 regulatory subunit 1B [KO:K15494 ]
24668 Ppp1ca; serine/threonine-protein phosphatase PP1-alpha catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
24669 Ppp1cc; serine/threonine-protein phosphatase PP1-gamma catalytic subunit isoform 1 [KO:K06269 ] [EC:3.1.3.16 ]
25594 Ppp1cb; serine/threonine-protein phosphatase PP1-beta catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
81646 Creb1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870 ]
81647 Atf2; cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
79255 Atf4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
310616 Creb3l4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048 ]
362165 Creb3l1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
362339 Creb3l2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
314638 Creb3l3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
500131 Creb5; cyclic AMP-responsive element-binding protein 5 [KO:K09047 ]
406169 Atf6b; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
54323 Arc; activity-regulated cytoskeleton-associated protein [KO:K15867 ]
24675 Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348 ] [EC:3.1.3.16 ]
171378 Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
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 pathway
KO pathway
LinkDB
All DBs