Entry Name Cocaine addiction - Vulpes lagopus (Arctic fox)
Description Drug addiction is a chronic, relapsing disorder in which compulsive drug-seeking and drug-taking behavior persists despite serious negative consequences.There is strong evidence that the dopaminergic system that projects from the ventral tegmental area (VTA) of the midbrain to the nucleus accumbens (NAc), and to other forebrain sites, is the major substrate of reward and reinforcement for both natural rewards and addictive drugs. Cocaine binds strongly to the dopamine-reuptake transporter, preventing the reuptake of dopamine into the nerve terminal. Because of this blocking effect, dopamine remains at high concentrations in the synapse and continues to affect adjacent neurons, producing the characteristic cocaine "high." Activated D1 receptor activates the PKA signaling pathway, and this pathway plays a critical role in mediating the behavioral responses to cocaine administration. Cocaine-induced neuroadaptations, including dopamine depletion, may underlie craving and hedonic dysregulation.
Class Human Diseases; Substance dependenceBRITE hierarchy
Pathway map Ortholog table Other DBs Organism Vulpes lagopus (Arctic fox) [GN:
vlg ]
Gene 121484057 SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155 ]
121477472 SLC6A3; sodium-dependent dopamine transporter isoform X1 [KO:K05036 ]
121477898 guanine nucleotide-binding protein G(s) subunit alpha isoform X1 [KO:K04632 ]
121471255 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
121487463 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
121495419 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
121480493 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
121501564 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
121492052 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
121489094 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
121484743 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
121501517 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
121494424 CREB3; cyclic AMP-responsive element-binding protein 3 isoform X1 [KO:K09048 ]
121494648 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
121474745 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
121500790 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
121492781 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
121473250 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
121472747 GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211 ]
121495448 GRIN3A; glutamate receptor ionotropic, NMDA 3A isoform X1 [KO:K05213 ]
121494970 GRIN3B; glutamate receptor ionotropic, NMDA 3B isoform X1 [KO:K05214 ]
121474112 PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494 ]
Compound C00355 3,4-Dihydroxy-L-phenylalanine
C01161 3,4-Dihydroxyphenylacetate
Reference Authors Ron D, Jurd R
Title The "ups and downs" of signaling cascades in addiction.
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 Chen JC, Chen PC, Chiang YC
Title Molecular mechanisms of psychostimulant addiction.
Journal Chang Gung Med J 32:148-54 (2009)
Reference Authors Nestler EJ
Title Is there a common molecular pathway for addiction?
Journal Reference Authors Bowers MS, McFarland K, Lake RW, Peterson YK, Lapish CC, Gregory ML, Lanier SM, Kalivas PW
Title Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking.
Journal Reference Authors Rahman Z, Schwarz J, Gold SJ, Zachariou V, Wein MN, Choi KH, Kovoor A, Chen CK, DiLeone RJ, Schwarz SC, Selley DE, Sim-Selley LJ, Barrot M, Luedtke RR, Self D, Neve RL, Lester HA, Simon MI, Nestler EJ
Title RGS9 modulates dopamine signaling in the basal ganglia.
Journal Reference Authors Horger BA, Iyasere CA, Berhow MT, Messer CJ, Nestler EJ, Taylor JR
Title Enhancement of locomotor activity and conditioned reward to cocaine by brain-derived neurotrophic factor.
Journal Reference Authors Mash DC, Pablo J, Ouyang Q, Hearn WL, Izenwasser S
Title Dopamine transport function is elevated in cocaine users.
Journal Reference Authors McClung CA, Nestler EJ
Title Regulation of gene expression and cocaine reward by CREB and DeltaFosB.
Journal Reference Authors McClung CA, Ulery PG, Perrotti LI, Zachariou V, Berton O, Nestler EJ
Title DeltaFosB: a molecular switch for long-term adaptation in the brain.
Journal Reference Authors Ang E, Chen J, Zagouras P, Magna H, Holland J, Schaeffer E, Nestler EJ
Title Induction of nuclear factor-kappaB in nucleus accumbens by chronic cocaine administration.
Journal Reference Authors Bibb JA, Chen J, Taylor JR, Svenningsson P, Nishi A, Snyder GL, Yan Z, Sagawa ZK, Ouimet CC, Nairn AC, Nestler EJ, Greengard P
Title Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5.
Journal Reference Authors Chao J, Nestler EJ
Title Molecular neurobiology of drug addiction.
Journal Related KO pathway LinkDB All DBs
