Entry
Name
Alcoholism
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 dependence
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Ortholog table
Disease
Other DBs
Orthology
K08155 MFS transporter, DHA1 family, solute carrier family 18 (vesicular amine transporter), member 1/2
K05036 solute carrier family 6 (neurotransmitter transporter, dopamine) member 3
K05208 glutamate receptor ionotropic, NMDA 1
K05209 glutamate receptor ionotropic, NMDA 2A
K05210 glutamate receptor ionotropic, NMDA 2B
K05211 glutamate receptor ionotropic, NMDA 2C
K05212 glutamate receptor ionotropic, NMDA 2D
K05213 glutamate receptor ionotropic, NMDA 3A
K05214 glutamate receptor ionotropic, NMDA 3B
K04632 guanine nucleotide-binding protein G(s) subunit alpha
K04630 guanine nucleotide-binding protein G(i) subunit alpha
K04534 guanine nucleotide-binding protein G(o) subunit alpha
K04536 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825 guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538 guanine nucleotide-binding protein subunit beta-4
K04539 guanine nucleotide-binding protein subunit beta-5
K07826 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548 guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K15014 solute carrier family 29 (equilibrative nucleoside transporter), member 1/2/3
K05870 cyclic AMP-responsive element-binding protein 1
K04450 cyclic AMP-dependent transcription factor ATF-2
K04374 cyclic AMP-dependent transcription factor ATF-4
K09048 cyclic AMP-responsive element-binding protein 3
K09047 cyclic AMP-responsive element-binding protein 5
K09049 cyclic AMP-dependent transcription factor ATF-6 beta
K05256 corticotropin-releasing hormone
K04355 brain-derived neurotrophic factor
K06279 SHC-transforming protein 1
K17447 SHC-transforming protein 2
K17448 SHC-transforming protein 3
K17449 SHC-transforming protein 4
K04364 growth factor receptor-bound protein 2
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K15840 proenkephalin B (prodynorphin)
K15494 protein phosphatase 1 regulatory subunit 1B
K06269 serine/threonine-protein phosphatase PP1 catalytic subunit [EC:3.1.3.16 ]
K15985 cAMP-dependent protein kinase inhibitor alpha
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
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