Skip to main content

Advertisement

Log in

Genetic approaches to alcohol addiction: gene expression studies and recent candidates from Drosophila

  • Review
  • Published:
Invertebrate Neuroscience

Abstract

Ethanol intake causes gene expression changes resulting in cellular and molecular adaptations that could be associated with a predisposition to alcohol dependence. Recently, several research groups have used high-throughput gene expression profiling to search for alcohol-responsive genes in Drosophila melanogaster. Comparison of data from these studies highlights the functional similarities in their results despite differences in their experimental approach and selection cases. Notably, alcohol-responsive gene sets associated with stress response, olfaction, metabolism, proteases, transcriptional regulation, regulation of signal transduction, nucleic acid binding and cytoskeletal organisation were markedly common to these studies. These data support the view that changes in gene expression in alcoholics are associated with widespread cellular functions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aroor AR, Shukla SD (2004) MAP kinase signaling in diverse effects of ethanol. Life Sci 74:2339–2364

    Article  PubMed  CAS  Google Scholar 

  • Atkinson NS (2009) Tolerance in Drosophila. J Neurogenet 23:293–302

    Article  PubMed  Google Scholar 

  • Bellen HJ, Levis RW, Liao G, He Y, Carlson JW, Tsang G, Evans-Holm M, Hiesinger PR, Schulze KL, Rubin GM, Hoskins RA, Spradling AC (2004) The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes. Genetics 167:761–781

    Article  PubMed  CAS  Google Scholar 

  • Berger KH, Kong EC, Dubnau J, Tully T, Moore MS, Heberlein U (2008) Ethanol sensitivity and tolerance in long-term memory mutants of Drosophila melanogaster. Alcohol Clin Exp Res 32:895–908

    Article  PubMed  CAS  Google Scholar 

  • Bjork K, Saarikoski TS, Arlinde C, Kovanen L, Osei-Hyiaman D, Ubaldi M, Reimers M, Hyytia P, Heilig M, Sommer WH (2006) Glutathione-S-transferase expression in the brain: possible role in ethanol preference and longevity. FASEB J 20:1826–1835

    Article  PubMed  CAS  Google Scholar 

  • Calabrese V, Renis M, Calderone A, Russo A, Barcellona ML, Rizza V (1996) Stress proteins and SH-goups in oxidant-induced cell damage after acute ethanol administration in rat. Free Radical Bio Med 20:391–397

    Article  CAS  Google Scholar 

  • Devineni AV, Heberlein H (2009) Preferential ethanol consumption in Drosophila models features of addiction. Curr Biol 19:2126–2132

    Article  PubMed  CAS  Google Scholar 

  • Devineni AV, Heberlein H (2010) Addiction-like behaviour in Drosophila. Commun Integr Biol 3:357–359

    Article  PubMed  Google Scholar 

  • Flatscher-Bader T, MPvd Brug, Landis N, Hwang JW, Harrison E, Wilce PA (2006) Comparative gene expression in brain regions of human alcoholics. Genes Brain Behav 5:78–84

    Article  PubMed  CAS  Google Scholar 

  • Guarnieri DJ, Heberlein U (2003) Drosophila melanogaster, a genetic model system for alcohol research. Int Rev Neurobiol 54:199–228

    Article  PubMed  CAS  Google Scholar 

  • Hallem EA, Dahanukar A, Carlson JR (2006) Insect odor and taste receptors. Annu Rev Entomol 51:113–135

    Article  PubMed  CAS  Google Scholar 

  • Heberlein U (2000) Genetics of alcohol-induced behaviors in Drosophila. Alcohol Res Health 24:185–188

    PubMed  CAS  Google Scholar 

  • Heberlein U, Wolf FW, Rothenfluh A, Guarnieri DJ (2004) Molecular genetic analysis of ethanol intoxication in Drosophila melanogaster. Integr Comp Biol 44:269–274

    Article  CAS  Google Scholar 

  • Jackson ES, Wayland MT, Fitzgerald W, Bahn S (2005) A microarray data analysis framework for post-mortem tissues. Methods 37:247–260

    Article  PubMed  CAS  Google Scholar 

  • Kareken DA, Claus ED, Sabri M, Dzemidzic M, Kosobud AE, Radnovich AJ, Hector D, Ramchandani VA, O’Connor SJ, Lowe M, Li TK (2004) Alcohol-related olfactory cues activate the nucleus accumbens and ventral tegmental area in high-risk drinkers: preliminary findings. Alcohol Clin Exp Res 28:550–557

    Article  PubMed  Google Scholar 

  • Kim YK, Lee BC, Ham BJ, Yang BH, Roh S, Choi J, Kang TC, Chai YG, Choi IG (2009) Increased transforming growth factor-beta1 in alcohol dependence. J Korean Med Sci 24:941–944

    Article  PubMed  CAS  Google Scholar 

  • Kong EC, Allouche L, Chapot PA, Vranizan K, Moore MS, Heberlein U, Wolf FW (2010) Ethanol-regulated genes that contribute to ethanol sensitivity and rapid ethanol tolerance in Drosophila. Alcohol Clin Exp Res 34:302–316

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Nahm M, Lee M, Kwon M, Kim E, Zadeh AD, Cao H, Kim HJ, Lee ZH, Oh SB, Yim J, Kolodziej PA, Lee S (2007) The F-actin-microtubule crosslinker shot is a platform for Krasavietz-mediated translational regulation of midline axon repulsion. Development 134:1767–1777

    Article  PubMed  CAS  Google Scholar 

  • Lockhart DJ, Dong H, Bryne MC, Follettie MT, Gallo MV, Chee MS, Mittmann M, Wang C, Kobayashi M, Horton H, Brown EL (1996) Expression monitoring by hybridisation to high density oligonucleotide arrays. Nat Biotechnol 14:1673–1680

    Article  Google Scholar 

  • Luo Z, Geschwind DH (2001) Microarray applications in neuroscience. Neurobiol Dis 8:183–193

    Article  PubMed  CAS  Google Scholar 

  • Mackay TF, Anholt RR (2006) Of flies and man: Drosophila as a model for human complex traits. Annu Rev Genomics Hum Genet 7:339–367

    Article  PubMed  CAS  Google Scholar 

  • Miles MF, Diaz JE, DeGuzman VS (1991) Mechanisms of neuronal adaptation to ethanol. Ethanol induces Hsc70 gene transcription in NG108–15 neuroblastoma x glioma cells. J Biol Chem 266:2409–2414

    PubMed  CAS  Google Scholar 

  • Moore MS, DeZazzo J, Luk AY, Tully T, Singh CM, Heberlein U (1998) Ethanol intoxication in Drosophila: genetic and pharmacological evidence for regulation by the cAMP signaling pathway. Cell 93:997–1007

    Article  PubMed  CAS  Google Scholar 

  • Morozova TV, Anholt RR, Mackay TF (2006) Transcriptional response to alcohol exposure in Drosophila melanogaster. Genome Biol 7:R95

    Article  PubMed  Google Scholar 

  • Morozova TV, Anholt RR, Mackay TF (2007) Phenotypic and transcriptional response to selection for alcohol sensitivity in Drosophila melanogaster. Genome Biol 8:R231

    Article  PubMed  Google Scholar 

  • Mulligan MK, Ponomarev I, Hitzemann RJ, Belknap JK, Tabakoff B, Harris RA, Crabbe JC, Blednov YA, Grahame NJ, Phillips TJ, Finn DA, Hoffman PL, Iyer VR, Koob GF, Bergeson SE (2006) Toward understanding the genetics of alcohol drinking through transcriptome meta-analysis. Proc Natl Acad Sci USA 103:6368–6373

    Article  PubMed  CAS  Google Scholar 

  • Omar R, Papolla M, Saran B (1990) Immunocytochemical detection of the 70kd-heat shock protein in alcoholic liver disease. Arch Pathol Lab Med 114:589–592

    PubMed  CAS  Google Scholar 

  • Parks AL, Cook KR, Belvin M et al (2004) Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat Genet 36:288–292

    Article  PubMed  CAS  Google Scholar 

  • Pignataro L, Miller AN, Ma L, Midha S, Protiva P, Herrera DG, Harrison NL (2007) Alcohol regulates gene expression in neurons via activation of heat shock factor 1. J Neurosci 27:12957–12966

    Article  PubMed  CAS  Google Scholar 

  • Raychoudhuri S, Sutphin PD, Chang JT, Altman RB (2001) Basic microarray analysis: grouping and feature reduction. Trends Biotechnol 19:189–193

    Article  Google Scholar 

  • Reiling JH, Doepfner KT, Hafen E, Stocker H (2005) Diet-dependent effects of the Drosophila Mnk1/Mnk2 homolog Lk6 on growth via eIF4E. Curr Biol 15:24–30

    Article  PubMed  CAS  Google Scholar 

  • Rubin GM et al (2000) Comparative genomics of the eukaryotes. Science 287:2204–2215

    Article  PubMed  CAS  Google Scholar 

  • Scholz H, Ramond J, Singh CM, Heberlein U (2000) Functional ethanol tolerance in Drosophila. Neuron 28:261–271

    Article  PubMed  CAS  Google Scholar 

  • Scholz H, Franz M, Heberlein U (2005) The hangover gene defines a stress pathway required for ethanol tolerance development. Nature 436:845–847

    Article  PubMed  CAS  Google Scholar 

  • Singh CM, Heberlein U (2000) Genetic control of acute ethanol-induced behaviors in Drosophila. Alcohol Clin Exp Res 24:1127–1136

    Article  PubMed  CAS  Google Scholar 

  • Spanagel R (2009) Alcoholism: a systems approach from molecular physiology to addictive behavior. Physiol Rev 89:649–705

    Article  PubMed  CAS  Google Scholar 

  • Tang AH, Tu CP (1994) Biochemical characterization of Drosophila glutathione S-transferases D1 and D21. J Biol Chem 269:27876–27884

    PubMed  CAS  Google Scholar 

  • Tomfohr J, Lu J, Kepler T (2005) Pathway level analysis of gene expression using singular value decomposition. BMC Bioinformatics 6:225

    Article  PubMed  Google Scholar 

  • Tsuchida S, Sato K (1992) Glutathione transferases and cancer. Crit Rev Biochem Mol 27:337–384

    Article  CAS  Google Scholar 

  • Tsuneizumi K, Nakayama T, Kamoshida Y, Kornberg TB, Christian JL, Tabata T (1997) Daughters against dpp modulates dpp organizing activity in Drosophila wing development. Nature 389:627–631

    Article  PubMed  CAS  Google Scholar 

  • Urban S, Lee JR, Freeman M (2002) A family of Rhomboid intramembrane proteases activates all Drosophila membrane-tethered EGF ligands. EMBO J 21:4277–4286

    Article  PubMed  CAS  Google Scholar 

  • Urizar NL, Yang Z, Edenberg HJ, Davis RL (2007) Drosophila Homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance. J Neurosci 27:4541–4551

    Article  PubMed  CAS  Google Scholar 

  • Waxman DJ, Azaroff L (1992) Phenobarbital induction of cytochrome P-450 gene expression. Biochem J 281:577–592

    PubMed  CAS  Google Scholar 

  • Wolf FW, Heberlein U (2003) Invertebrate models of drug abuse. J Neurobiol 54:161–178

    Article  PubMed  CAS  Google Scholar 

  • Wolf FW, Rodan AR, Tsai LT, Heberlein U (2002) High-resolution analysis of ethanol-induced locomotor stimulation in Drosophila. J Neurosci 22:11035–11044

    PubMed  CAS  Google Scholar 

  • Worst TJ, Vrana KE (2005) Alcohol and gene expression in the central nervous system. Alcohol Alcohol 40:63–75

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by a fellowship grant from the Tai Solarin University of Education. The author expresses appreciation for reviewers’ insightful comments and suggestions.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Awoyemi A. Awofala.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLS 68 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Awofala, A.A. Genetic approaches to alcohol addiction: gene expression studies and recent candidates from Drosophila . Invert Neurosci 11, 1–7 (2011). https://doi.org/10.1007/s10158-010-0113-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10158-010-0113-y

Keywords

Navigation