Entry Name Alcoholism - Microcebus murinus (gray mouse lemur)
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 Microcebus murinus (gray mouse lemur) [GN:
mmur ]
Gene 105855818 GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
105856485 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
105858143 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta isoform X1 [KO:K09049 ]
105858535 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
105859108 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 [KO:K09048 ]
105859532 SLC29A1; equilibrative nucleoside transporter 1 isoform X1 [KO:K15014 ]
105861782 GNG5; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5 [KO:K04542 ]
105864008 GNAI3; guanine nucleotide-binding protein G(k) subunit alpha [KO:K04630 ]
105864304 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
105865052 ATF2; LOW QUALITY PROTEIN: cyclic AMP-dependent transcription factor ATF-2 [KO:K04450 ]
105865636 GRIN2D; glutamate receptor ionotropic, NMDA 2D isoform X1 [KO:K05212 ]
105866545 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
105867542 SLC29A2; equilibrative nucleoside transporter 2 isoform X1 [KO:K15014 ]
105867677 GNG2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2 [KO:K07826 ]
105868427 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 isoform X1 [KO:K04537 ]
105869000 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 isoform X2 [KO:K07825 ]
105870183 SLC29A3; equilibrative nucleoside transporter 3 isoform X1 [KO:K15014 ]
105870695 GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
105872857 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
105873936 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
105873983 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
105874305 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
105874990 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
105876449 SLC6A3; sodium-dependent dopamine transporter isoform X1 [KO:K05036 ]
105877661 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
105877681 CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
105878586 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
105879338 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
105880930 PPP1CC; LOW QUALITY PROTEIN: serine/threonine-protein phosphatase PP1-gamma catalytic subunit [KO:K06269 ] [EC:3.1.3.16 ]
105882560 SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155 ]
105882598 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
105885209 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
105885942 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 [KO:K09048 ]
109729475 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
109729570 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
109729970 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
109731176 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 [KO:K04545 ]
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
