Entry Name Cocaine addiction - Delphinapterus leucas (beluga whale)
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 Other DBs Organism Delphinapterus leucas (beluga whale) [GN:
dle ]
Gene 111164599 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
111166195 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 [KO:K09048 ]
111166488 PPP1R1B; protein phosphatase 1 regulatory subunit 1B isoform X1 [KO:K15494 ]
111167181 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
111170472 GRIN3B; glutamate receptor ionotropic, NMDA 3B isoform X1 [KO:K05214 ]
111170946 ATF6B; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
111171769 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
111172270 SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155 ]
111172890 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
111174368 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
111176991 GRIN1; glutamate receptor ionotropic, NMDA 1 isoform X1 [KO:K05208 ]
111177035 GPSM1; LOW QUALITY PROTEIN: G-protein-signaling modulator 1 [KO:K15839 ]
111177962 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
111179110 NFKB1; nuclear factor NF-kappa-B p105 subunit isoform X1 [KO:K02580 ]
111179820 BDNF; LOW QUALITY PROTEIN: brain-derived neurotrophic factor [KO:K04355 ]
111180070 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha [KO:K04630 ]
111180225 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
111180666 GRIN2D; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 2D [KO:K05212 ]
111182859 GRIN2C; glutamate receptor ionotropic, NMDA 2C isoform X1 [KO:K05211 ]
111183987 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 [KO:K09048 ]
111186212 ATF4; cyclic AMP-dependent transcription factor ATF-4 isoform X1 [KO:K04374 ]
111186741 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632 ]
111188007 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
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
