Entry
Name
Alcoholism - Myotis lucifugus (little brown bat)
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
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Myotis lucifugus (little brown bat) [GN:
mlf ]
Gene
102438995 SLC18A2; synaptic vesicular amine transporter isoform X1 [KO:K08155 ]
102436175 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
102430817 GRIN3A; LOW QUALITY PROTEIN: glutamate receptor ionotropic, NMDA 3A [KO:K05213 ]
102425604 GRIN3B; glutamate receptor ionotropic, NMDA 3B isoform X1 [KO:K05214 ]
102428502 GNAS; guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X11 [KO:K04632 ]
102427230 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
102429580 guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
102431273 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
102438598 guanine nucleotide-binding protein G(o) subunit alpha-like [KO:K04534 ]
102420431 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
102420482 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
102428334 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
102431535 GNB4; guanine nucleotide-binding protein subunit beta-4 isoform X1 [KO:K04538 ]
102420203 GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
102441805 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
102442437 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
102428001 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
102422498 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
106697041 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
102432910 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
102432599 GNG14; putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
102428066 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
102431853 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
102432692 guanine nucleotide-binding protein G(T) subunit gamma-T1-like [KO:K04548 ]
102420164 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
102435777 SLC29A2; equilibrative nucleoside transporter 2 isoform X2 [KO:K15014 ]
102419013 SLC29A1; equilibrative nucleoside transporter 1 isoform X1 [KO:K15014 ]
102428529 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
102418405 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
102429560 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
102431250 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
102416978 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X2 [KO:K09048 ]
102443216 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
102427186 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
102421849 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
102439961 CREB5; cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
102428756 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
102435382 SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448 ]
102431548 SHC4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449 ]
102421027 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
102426645 CALML4; LOW QUALITY PROTEIN: calmodulin-like protein 4 [KO:K02183 ]
102429857 PPP1CA; serine/threonine-protein phosphatase PP1-alpha catalytic subunit isoform X2 [KO:K06269 ] [EC:3.1.3.16 ]
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 pathway
KO pathway
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