Entry Name Cocaine addiction - Mus musculus (house mouse)
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 Mus musculus (house mouse) [GN:
mmu ]
Gene 110877 Slc18a1; solute carrier family 18 (vesicular monoamine), member 1 [KO:K08155 ]
11909 Atf2; activating transcription factor 2 [KO:K04450 ]
11911 Atf4; activating transcription factor 4 [KO:K04374 ]
12064 Bdnf; brain derived neurotrophic factor [KO:K04355 ]
12569 Cdk5r1; cyclin dependent kinase 5, regulatory subunit 1 [KO:K11716 ]
12912 Creb1; cAMP responsive element binding protein 1 [KO:K05870 ]
12913 Creb3; cAMP responsive element binding protein 3 [KO:K09048 ]
12915 Atf6b; activating transcription factor 6 beta [KO:K09049 ]
13162 Slc6a3; solute carrier family 6 (neurotransmitter transporter, dopamine), member 3 [KO:K05036 ]
13385 Dlg4; discs large MAGUK scaffold protein 4 [KO:K11828 ]
14800 Gria2; glutamate receptor, ionotropic, AMPA2 (alpha 2) [KO:K05198 ]
14810 Grin1; glutamate receptor, ionotropic, NMDA1 (zeta 1) [KO:K05208 ]
14811 Grin2a; glutamate receptor, ionotropic, NMDA2A (epsilon 1) [KO:K05209 ]
14812 Grin2b; glutamate receptor, ionotropic, NMDA2B (epsilon 2) [KO:K05210 ]
14813 Grin2c; glutamate receptor, ionotropic, NMDA2C (epsilon 3) [KO:K05211 ]
14814 Grin2d; glutamate receptor, ionotropic, NMDA2D (epsilon 4) [KO:K05212 ]
170483 Grin3b; glutamate receptor, ionotropic, NMDA3B [KO:K05214 ]
18033 Nfkb1; nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105 [KO:K02580 ]
19049 Ppp1r1b; protein phosphatase 1, regulatory inhibitor subunit 1B [KO:K15494 ]
19697 Rela; v-rel reticuloendotheliosis viral oncogene homolog A (avian) [KO:K04735 ]
19739 Rgs9; regulator of G-protein signaling 9 [KO:K13765 ]
208647 Creb3l2; cAMP responsive element binding protein 3-like 2 [KO:K09048 ]
208677 Creb3l3; cAMP responsive element binding protein 3-like 3 [KO:K09048 ]
214084 Slc18a2; solute carrier family 18 (vesicular monoamine), member 2 [KO:K08155 ]
231991 Creb5; cAMP responsive element binding protein 5 [KO:K09047 ]
242443 Grin3a; glutamate receptor ionotropic, NMDA3A [KO:K05213 ]
26427 Creb3l1; cAMP responsive element binding protein 3-like 1 [KO:K09048 ]
67839 Gpsm1; G-protein signalling modulator 1 (AGS3-like, C. elegans) [KO:K15839 ]
78284 Creb3l4; cAMP responsive element binding protein 3-like 4 [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
