Signaling Pathways Mediating Alcohol Effects

Overview

Journal Curr Top Behav Neurosci

Publisher Springer

Specialty Psychology

Date 2011 Aug 31

PMID 21877259

Citations 60

Authors

Dorit Ron

Robert O Messing

Affiliations

Soon will be listed here.

Abstract

Ethanol's effects on intracellular signaling pathways contribute to acute effects of ethanol as well as to neuroadaptive responses to repeated ethanol exposure. In this chapter we review recent discoveries that demonstrate how ethanol alters signaling pathways involving several receptor tyrosine kinases and intracellular tyrosine and serine-threonine kinases, with consequences for regulation of cell surface receptor function, gene expression, protein translation, neuronal excitability and animal behavior. We also describe recent work that demonstrates a key role for ethanol in regulating the function of scaffolding proteins that organize signaling complexes into functional units. Finally, we review recent exciting studies demonstrating ethanol modulation of DNA and histone modification and the expression of microRNAs, indicating epigenetic mechanisms by which ethanol regulates neuronal gene expression and addictive behaviors.

Citing Articles

Proteomic Analysis of Chronic Binge Alcohol-Induced Hippocampal and Anterior Cingulate Cortex Neuroadaptations in Simian Immunodeficiency Virus (SIV)-Infected Female Rhesus Macaques.

Fitzpatrick-Schmidt T, Mansouri A, Adamec J, Klein J, Coleman L, Edwards K J Neuroimmune Pharmacol. 2025; 20(1):16.

PMID: 39930298 DOI: 10.1007/s11481-025-10179-5.

Targeting of CYP2E1 by miRNAs in alcohol-induced intestine injury.

Mun H, Lee S, Choi S, Jeong J, Ko S, Chun Y Mol Cells. 2024; 47(7):100074.

PMID: 38901530 PMC: 11267015. DOI: 10.1016/j.mocell.2024.100074.

Using epigenomics to understand cellular responses to environmental influences in diseases.

Wattacheril J, Raj S, Knowles D, Greally J PLoS Genet. 2023; 19(1):e1010567.

PMID: 36656803 PMC: 9851565. DOI: 10.1371/journal.pgen.1010567.

Genome-wide transcriptomics of the amygdala reveals similar oligodendrocyte-related responses to acute and chronic alcohol drinking in female mice.

Narendra S, Klengel C, Hamzeh B, Patel D, Otten J, Lardenoije R Transl Psychiatry. 2022; 12(1):476.

PMID: 36371333 PMC: 9653459. DOI: 10.1038/s41398-022-02231-2.

Acute Intoxication With Alcohol Reduces Trauma-Induced Proinflammatory Response and Barrier Breakdown in the Lung the Wnt/β-Catenin Signaling Pathway.

Noack L, Bundkirchen K, Xu B, Gylstorff S, Zhou Y, Kohler K Front Immunol. 2022; 13:866925.

PMID: 35663960 PMC: 9159919. DOI: 10.3389/fimmu.2022.866925.

References

Yoshii A, Constantine-Paton M . Postsynaptic BDNF-TrkB signaling in synapse maturation, plasticity, and disease. Dev Neurobiol. 2010; 70(5):304-22. PMC: 2923204. DOI: 10.1002/dneu.20765. View

Yin H, Ostlund S, Knowlton B, Balleine B . The role of the dorsomedial striatum in instrumental conditioning. Eur J Neurosci. 2005; 22(2):513-23. DOI: 10.1111/j.1460-9568.2005.04218.x. View

Chandler L, Sutton G . Acute ethanol inhibits extracellular signal-regulated kinase, protein kinase B, and adenosine 3':5'-cyclic monophosphate response element binding protein activity in an age- and brain region-specific manner. Alcohol Clin Exp Res. 2005; 29(4):672-82. DOI: 10.1097/01.alc.0000158935.53360.5f. View

Yao L, Arolfo M, Dohrman D, Jiang Z, Fan P, Fuchs S . betagamma Dimers mediate synergy of dopamine D2 and adenosine A2 receptor-stimulated PKA signaling and regulate ethanol consumption. Cell. 2002; 109(6):733-43. DOI: 10.1016/s0092-8674(02)00763-8. View

Pascoli V, Besnard A, Herve D, Pages C, Heck N, Girault J . Cyclic adenosine monophosphate-independent tyrosine phosphorylation of NR2B mediates cocaine-induced extracellular signal-regulated kinase activation. Biol Psychiatry. 2010; 69(3):218-27. DOI: 10.1016/j.biopsych.2010.08.031. View

Kouzarides T . Chromatin modifications and their function. Cell. 2007; 128(4):693-705. DOI: 10.1016/j.cell.2007.02.005. View

Thomas U . Modulation of synaptic signalling complexes by Homer proteins. J Neurochem. 2002; 81(3):407-13. DOI: 10.1046/j.1471-4159.2002.00869.x. View

Beggs H, Soriano P, Maness P . NCAM-dependent neurite outgrowth is inhibited in neurons from Fyn-minus mice. J Cell Biol. 1994; 127(3):825-33. PMC: 2120232. DOI: 10.1083/jcb.127.3.825. View

Jiang Z, Ye J . Protein kinase C epsilon is involved in ethanol potentiation of glycine-gated Cl(-) current in rat neurons of ventral tegmental area. Neuropharmacology. 2003; 44(4):493-502. DOI: 10.1016/s0028-3908(02)00409-4. View

10.

Hermanto U, Zong C, Li W, Wang L . RACK1, an insulin-like growth factor I (IGF-I) receptor-interacting protein, modulates IGF-I-dependent integrin signaling and promotes cell spreading and contact with extracellular matrix. Mol Cell Biol. 2002; 22(7):2345-65. PMC: 133698. DOI: 10.1128/MCB.22.7.2345-2365.2002. View

11.

Lu L, Koya E, Zhai H, Hope B, Shaham Y . Role of ERK in cocaine addiction. Trends Neurosci. 2006; 29(12):695-703. DOI: 10.1016/j.tins.2006.10.005. View

12.

Jeanblanc J, He D, McGough N, Logrip M, Phamluong K, Janak P . The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption. J Neurosci. 2006; 26(5):1457-64. PMC: 6675490. DOI: 10.1523/JNEUROSCI.3786-05.2006. View

13.

Pandey S, Zhang H, Roy A, Misra K . Central and medial amygdaloid brain-derived neurotrophic factor signaling plays a critical role in alcohol-drinking and anxiety-like behaviors. J Neurosci. 2006; 26(32):8320-31. PMC: 6673799. DOI: 10.1523/JNEUROSCI.4988-05.2006. View

14.

Gordon A, Yao L, Wu Z, Coe I, Diamond I . Ethanol alters the subcellular localization of delta- and epsilon protein kinase C in NG108-15 cells. Mol Pharmacol. 1997; 52(4):554-9. DOI: 10.1124/mol.52.4.554. View

15.

Rong R, Ahn J, Huang H, Nagata E, Kalman D, Kapp J . PI3 kinase enhancer-Homer complex couples mGluRI to PI3 kinase, preventing neuronal apoptosis. Nat Neurosci. 2003; 6(11):1153-61. DOI: 10.1038/nn1134. View

16.

Brodie M, Shefner S, Dunwiddie T . Ethanol increases the firing rate of dopamine neurons of the rat ventral tegmental area in vitro. Brain Res. 1990; 508(1):65-9. DOI: 10.1016/0006-8993(90)91118-z. View

17.

Corl A, Berger K, Ophir-Shohat G, Gesch J, Simms J, Bartlett S . Happyhour, a Ste20 family kinase, implicates EGFR signaling in ethanol-induced behaviors. Cell. 2009; 137(5):949-60. DOI: 10.1016/j.cell.2009.03.020. View

18.

NISHIZUKA Y . Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 1995; 9(7):484-96. View

19.

Khasar S, Lin Y, Martin A, Dadgar J, McMahon T, Wang D . A novel nociceptor signaling pathway revealed in protein kinase C epsilon mutant mice. Neuron. 2000; 24(1):253-60. PMC: 11587340. DOI: 10.1016/s0896-6273(00)80837-5. View

20.

Pandey S, Zhang H, Roy A, Xu T . Deficits in amygdaloid cAMP-responsive element-binding protein signaling play a role in genetic predisposition to anxiety and alcoholism. J Clin Invest. 2005; 115(10):2762-73. PMC: 1236671. DOI: 10.1172/JCI24381. View