Entry
Name
Alcoholism - Lemur catta (Ring-tailed 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 dependence
BRITE hierarchy
Pathway map
Ortholog table
Other DBs
Organism
Lemur catta (Ring-tailed lemur) [GN:
lcat ]
Gene
123626346 SLC18A1; chromaffin granule amine transporter isoform X1 [KO:K08155 ]
123632367 GRIN2A; glutamate receptor ionotropic, NMDA 2A isoform X1 [KO:K05209 ]
123634771 LOW QUALITY PROTEIN: uncharacterized protein LOC123634771 [KO:K11253 ]
123622310 guanine nucleotide-binding protein G(s) subunit alpha isoforms short isoform X1 [KO:K04632 ]
123623249 GNAI2; guanine nucleotide-binding protein G(i) subunit alpha-2 [KO:K04630 ]
123647150 GNAI1; guanine nucleotide-binding protein G(i) subunit alpha-1 [KO:K04630 ]
123635002 GNAI3; guanine nucleotide-binding protein G(i) subunit alpha-3 [KO:K04630 ]
123625313 GNAO1; guanine nucleotide-binding protein G(o) subunit alpha isoform X1 [KO:K04534 ]
123636000 GNB1; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 [KO:K04536 ]
123631640 GNB2; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2 [KO:K04537 ]
123640104 GNB3; guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 [KO:K07825 ]
123630284 GNB4; guanine nucleotide-binding protein subunit beta-4 [KO:K04538 ]
123622795 GNB5; guanine nucleotide-binding protein subunit beta-5 [KO:K04539 ]
123641343 GNG3; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3 [KO:K04540 ]
123627584 GNG4; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4 [KO:K04541 ]
123648542 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5-like [KO:K04542 ]
123633190 GNG7; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7 [KO:K04543 ]
123623917 GNG8; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8 [KO:K04544 ]
123646542 GNG10; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10 isoform X1 [KO:K04545 ]
123647376 GNG11; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11 [KO:K04546 ]
123637148 GNG14; LOW QUALITY PROTEIN: putative guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-14 [KO:K04347 ]
123635536 GNG12; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347 ]
123631427 GNG13; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13 [KO:K04547 ]
123647151 GNGT1; guanine nucleotide-binding protein G(T) subunit gamma-T1 [KO:K04548 ]
123620748 GNGT2; guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2 [KO:K04549 ]
123631933 SLC29A1; equilibrative nucleoside transporter 1 isoform X1 [KO:K15014 ]
123641901 SLC29A2; equilibrative nucleoside transporter 2 isoform X1 [KO:K15014 ]
123650389 SLC29A3; equilibrative nucleoside transporter 3 isoform X1 [KO:K15014 ]
123644073 CREB1; cyclic AMP-responsive element-binding protein 1 isoform X1 [KO:K05870 ]
123643408 ATF2; cyclic AMP-dependent transcription factor ATF-2 isoform X1 [KO:K04450 ]
123640339 ATF4; cyclic AMP-dependent transcription factor ATF-4 [KO:K04374 ]
123646158 CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048 ]
123647675 CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform X1 [KO:K09048 ]
123633885 CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform X1 [KO:K09048 ]
123634008 CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform X1 [KO:K09048 ]
123642645 CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform X1 [KO:K09048 ]
123647634 cyclic AMP-responsive element-binding protein 5 isoform X1 [KO:K09047 ]
123631772 ATF6B; cyclic AMP-dependent transcription factor ATF-6 beta [KO:K09049 ]
123642542 BDNF; LOW QUALITY PROTEIN: brain-derived neurotrophic factor [KO:K04355 ]
123634905 CALML6; LOW QUALITY PROTEIN: calmodulin-like protein 6 [KO:K02183 ]
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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