Entry Name Alcoholism - Tupaia chinensis (Chinese tree shrew)
Description Alcoholism, also called dependence on alcohol (ethanol), is a chronic relapsing disorder that is progressive and has serious detrimental health outcomes. As one of the primary mediators of the rewarding effects of alcohol, dopaminergic ventral tegmental area (VTA) projections to the nucleus accumbens (NAc) have been identified. Acute exposure to alcohol stimulates dopamine release into the NAc, which activates D1 receptors, stimulating PKA signaling and subsequent CREB-mediated gene expression, whereas chronic alcohol exposure leads to an adaptive downregulation of this pathway, in particular of CREB function. The decreased CREB function in the NAc may promote the intake of drugs of abuse to achieve an increase in reward and thus may be involved in the regulation of positive affective states of addiction. PKA signaling also affects NMDA receptor activity and may play an important role in neuroadaptation in response to chronic alcohol exposure.
Class Human Diseases; Substance dependenceBRITE hierarchy
Pathway map Disease Other DBs Organism Tupaia chinensis (Chinese tree shrew) [GN:
tup ]
Gene 102469683 GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208 ]
102471928 CREB3L2; cAMP responsive element binding protein 3 like 2 [KO:K09048 ]
102477222 SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099 ]
102478830 GRIN3A; glutamate ionotropic receptor NMDA type subunit 3A [KO:K05213 ]
102479118 GRIN2C; glutamate ionotropic receptor NMDA type subunit 2C [KO:K05211 ]
102482548 PPP1R1B; protein phosphatase 1 regulatory inhibitor subunit 1B [KO:K15494 ]
102483965 FOSB; FosB proto-oncogene, AP-1 transcription factor subunit [KO:K09029 ]
102484102 CREB3L3; cAMP responsive element binding protein 3 like 3 [KO:K09048 ]
102487806 GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210 ]
102487925 GRIN2A; glutamate ionotropic receptor NMDA type subunit 2A [KO:K05209 ]
102489563 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas [KO:K04632 ]
102491362 CREB3L1; cAMP responsive element binding protein 3 like 1 [KO:K09048 ]
102494629 SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099 ]
102494703 CREB3L4; cAMP responsive element binding protein 3 like 4 [KO:K09048 ]
102497931 SLC29A1; solute carrier family 29 member 1 (Augustine blood group) [KO:K15014 ]
102498157 GRIN2D; glutamate ionotropic receptor NMDA type subunit 2D [KO:K05212 ]
102499931 GRIN3B; glutamate ionotropic receptor NMDA type subunit 3B [KO:K05214 ]
Compound C00355 3,4-Dihydroxy-L-phenylalanine
C01161 3,4-Dihydroxyphenylacetate
Reference Authors Spanagel R
Title Alcoholism: a systems approach from molecular physiology to addictive behavior.
Journal Reference Authors Newton PM, Messing RO
Title Intracellular signaling pathways that regulate behavioral responses to ethanol.
Journal Reference Authors Mailliard WS, Diamond I
Title Recent advances in the neurobiology of alcoholism: the role of adenosine.
Journal Reference Authors Ron D, Jurd R
Title The "ups and downs" of signaling cascades in addiction.
Journal Reference Authors Diana M, Brodie M, Muntoni A, Puddu MC, Pillolla G, Steffensen S, Spiga S, Little HJ
Title Enduring effects of chronic ethanol in the CNS: basis for alcoholism.
Journal Reference Authors Moonat S, Starkman BG, Sakharkar A, Pandey SC
Title Neuroscience of alcoholism: molecular and cellular mechanisms.
Journal Reference Authors Pandey SC
Title The gene transcription factor cyclic AMP-responsive element binding protein: role in positive and negative affective states of alcohol addiction.
Journal Reference Authors Zhang TA, Maldve RE, Morrisett RA
Title Coincident signaling in mesolimbic structures underlying alcohol reinforcement.
Journal Reference Authors Maldve RE, Zhang TA, Ferrani-Kile K, Schreiber SS, Lippmann MJ, Snyder GL, Fienberg AA, Leslie SW, Gonzales RA, Morrisett RA
Title DARPP-32 and regulation of the ethanol sensitivity of NMDA receptors in the nucleus accumbens.
Journal Reference Authors Lovinger DM
Title NMDA receptors lose their inhibitions.
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 Berke JD, Hyman SE
Title Addiction, dopamine, and the molecular mechanisms of memory.
Journal Reference Authors Clapp P, Bhave SV, Hoffman PL
Title How Adaptation of the Brain to Alcohol Leads to Dependence: A Pharmacological Perspective.
Journal Alcohol Res Health 31:310-339 (2008)
Reference Authors Jeanes ZM, Buske TR, Morrisett RA
Title In vivo chronic intermittent ethanol exposure reverses the polarity of synaptic plasticity in the nucleus accumbens shell.
Journal Reference Authors Lee AM, Messing RO
Title Protein kinases and addiction.
Journal Reference Authors Repunte-Canonigo V, Lutjens R, van der Stap LD, Sanna PP
Title Increased expression of protein kinase A inhibitor alpha (PKI-alpha) and decreased PKA-regulated genes in chronic intermittent alcohol exposure.
Journal Reference Authors Logrip ML, Janak PH, Ron D
Title Dynorphin is a downstream effector of striatal BDNF regulation of ethanol intake.
Journal Reference Authors Shukla SD, Velazquez J, French SW, Lu SC, Ticku MK, Zakhari S
Title Emerging role of epigenetics in the actions of alcohol.
Journal Reference Authors Pascual M, Boix J, Felipo V, Guerri C
Title Repeated alcohol administration during adolescence causes changes in the mesolimbic dopaminergic and glutamatergic systems and promotes alcohol intake in the adult rat.
Journal Reference Authors Li J, Cheng Y, Bian W, Liu X, Zhang C, Ye JH
Title Region-specific induction of FosB/DeltaFosB by voluntary alcohol intake: effects of naltrexone.
Journal Related KO pathway
