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Differential expression of diacylglycerol kinase iota and L18A mRNAs in the brains of alcohol-preferring AA and alcohol-avoiding ANA rats

Abstract

Ethanol preference and behavioral disinhibition in AA (alcohol accepting) animals is a behavioral constellation similar to that seen in human type II alcoholism, for which considerable genetic loading has been shown. In search of novel neural substrates for this phenotype, we compared gene expression in the cerebral cortex of the AA rat with two groups of control animals, the ANA (alcohol non-accepting) line and heterogeneous Wistar animals, by differential display RT-PCR. We identified two transcripts, ribosomal protein L18a mRNA and diacyglycerol kinase iota mRNA, which are differentially expressed between AA and ANA rats. Ribosomal protein L18A mRNA is evenly expressed throughout the brain, but strongly reduced in cortex of AA rats vs controls. Diacylglycerol kinase iota is exclusively found in the brain, and expressed in a distinct regional pattern. Its cortical expression is about 25% higher in AA than ANA rats. Differential display RT-PCR seems to provide a feasible strategy to identify previously unknown genes whose differential expression correlates with behavioral phenotypes related to dependence.

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References

  1. Cloninger CR . Neurogenetic adaptive mechanisms in alcoholism Science 1987 236: 410–416

    Article  CAS  Google Scholar 

  2. Cloninger CR, Bohman M, Sigvardsson S . Inheritance of alcohol abuse. Cross-fostering analysis of adopted men Arch Gen Psychiatry 1981 38: 861–868

    Article  CAS  Google Scholar 

  3. Cloninger CR, Bohman M, Sigvardsson S, von Knorring AL . Psychopathology in adopted-out children of alcoholics. The Stockholm Adoption Study Recent Developments in Alcoholism 1985 3: 37–51

    Article  CAS  Google Scholar 

  4. Li TK, Lumeng L, McBride WJ, Murphy JM . Genetic and neurobiological basis of alcohol-seeking behavior Alcohol Alcohol 1994 29: 697–700

    CAS  PubMed  Google Scholar 

  5. Sinclair JD, Le AD, Kiianmaa K . The AA and ANA rat lines, selected for differences in voluntary alcohol consumption Experientia 1989 45: 798–805

    Article  CAS  Google Scholar 

  6. Li TK, Lumeng L, McBride WJ, Murphy JM . Rodent lines selected for factors affecting alcohol consumption Alcohol & Alcoholism 1987 Suppl 1: 91–96

    Google Scholar 

  7. Colombo G, Agabio R, Lobina C, Reali R, Zocchi A, Fadda F et al. Sardinian alcohol-preferring rats: a genetic animal model of anxiety Physiol Behav 1995 57: 1181–1185

    Article  CAS  Google Scholar 

  8. Hollway FA, Bird DC, McLean GA, Devenport J, Holloway JA, Tapp WN . Effects of cortical, hypothalamic, and hippocampal lesions on chronic alcohol intake and preference in rats Curr Alcoholism 1979 7: 123–130

    CAS  Google Scholar 

  9. Murphy JM, McBride WJ, Lumeng L, Li TK . Regional brain levels of monoamines in alcohol-preferring and -nonpreferring lines of rats Pharmacol Biochem Behav 1982 16: 145–149

    Article  CAS  Google Scholar 

  10. Chen F, Jarrott B, Lawrence AJ . Up-regulation of cortical AMPA receptor binding in the fawn-hooded rat following ethanol withdrawal Eur J Pharmacol 1999 384: 139–146

    Article  CAS  Google Scholar 

  11. Barbaccia ML, Affricano D, Trabucchi M, Purdy RH, Colombo G, Agabio R et al. Ethanol markedly increases ‘GABAergic’ neurosteroids in alcohol-preferring rats Eur J Pharmacol 1999 384: R1–R2

    Article  CAS  Google Scholar 

  12. Gianoulakis C, de Waele JP, Kiianmaa K . Differences in the brain and pituitary beta-endorphin system between the alcohol-preferring AA and alcohol-avoiding ANA rats Alcohol Clin Exp Res 1992 16: 453–459

    Article  CAS  Google Scholar 

  13. Soini SL, Honkanen A, Hyytia P, Korpi ER . [3H]ethylketocyclazocine binding to brain opioid receptor subtypes in alcohol-preferring AA and alcohol-avoiding ANA rats Alcohol 1999 18: 27–34

    Article  CAS  Google Scholar 

  14. Nylander I, Hyytia P, Forsander O, Terenius L . Differences between alcohol-preferring (AA) and alcohol-avoiding (ANA) rats in the prodynorphin and proenkephalin systems Alcohol Clin Exp Res 1994 18: 1272–1279

    Article  CAS  Google Scholar 

  15. Flanigan TP, Leslie RA . Changes in brain gene expression in psychiatric illness: mRNA differential display provides some clues Mol Psychiatry 1997 2: 451–456

    Article  CAS  Google Scholar 

  16. Möller C, Wiklund L, Thorsell A, Hyytia P, Heilig M . Decreased measures of experimental anxiety in rats bred for high alcohol preference Alcohol Clin Exp Res 1997 21: 656–660

    Article  Google Scholar 

  17. Liang P . Factors ensuring successful use of differential display Methods 1998 16: 361–364

    Article  CAS  Google Scholar 

  18. Fan L, van der Brug M, Chen W, Dodd PR, Matsumoto I, Niwa S et al. Increased expression of mitochondrial genes in human alcoholic brain revealed by differential display Alcohol Clin Exp Res 1999 23: 408–413

    Article  CAS  Google Scholar 

  19. Aoyama Y, Chan YL, Meyuhas O, Wool IG . The primary structure of rat ribosomal protein L18a FEBS Lett 1989 247: 242–246

    Article  CAS  Google Scholar 

  20. Dong G, Loukinova E, Smith CW, Chen Z, Van Waes C . Genes differentially expressed with malignant transformation and metastatic tumor progression of murine squamous cell carcinoma J Cell Biochem 1997 28–29: (Suppl) 90–100

    Article  Google Scholar 

  21. Wool IG . Extraribosomal functions of ribosomal proteins Trends Biochem Sci 1996 21: 164–165

    Article  CAS  Google Scholar 

  22. Gramatikoff K, Schaffner W, Georgiev O . The leucine zipper of c-Jun binds to ribosomal protein L18a: a role in Jun protein regulation? Biol Chem Hoppe-Seyler 1995 376: 321–325

    Article  CAS  Google Scholar 

  23. van Blitterswijk WJ, Houssa B . Diacylglycerol kinases in signal transduction Chem Phys Lipids 1999 98: 95–108

    Article  CAS  Google Scholar 

  24. Goto K, Kondo H . A 104-kDa diacylglycerol kinase containing ankyrin-like repeats localizes in the cell nucleus Proc Natl Acad Sci Us̄ 1996 93: 11196–11201

    Article  CAS  Google Scholar 

  25. Ding L, Traer E, McIntyre TM, Zimmerman GA, Prescott SM . The cloning and characterization of a novel human diacylglycerol kinase, DGKiota J Biol Chem 1998 273: 32746–32752

    Article  CAS  Google Scholar 

  26. Sigvardsson S, Bohman M, Cloninger CR . Replication of the Stockholm adoption study of alcoholism—confirmatory cross-fostering analysis Arch Gen Psychiatry 1996 53: 681–687

    Article  CAS  Google Scholar 

  27. Saito T, Hashimoto E, Ashizawa T, Kamada H, Ozawa H, Takahata N et al. Alcohol consumption and brain adenylate cyclase system in rats: brain adenylate cyclase activity in alcohol-preferring AA and alcohol-avoiding ANA rats. [Japanese] Arukoru Kenkyu-To Yakubutsu Ison Japanese Journal of Alcohol Studies & Drug Dependence 1993 28: 26–34

    CAS  Google Scholar 

  28. Sossin WS, Sacktor TC, Schwartz JH . Persistent activation of protein kinase C during the development of long-term facilitation in Aplysia Learning & Memory 1994 1: 189–202

    CAS  Google Scholar 

  29. Pierce RC, Quick EA, Reeder DC, Morgan ZR, Kalivas PW . Calcium-mediated second messengers modulate the expression of behavioral sensitization to cocaine J Pharmacol Exp Therapeut 1998 286: 1171–1176

    CAS  Google Scholar 

  30. Chomczynski P, Sacchi N . Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction Analyt Biochem 1987 162: 156–159

    Article  CAS  Google Scholar 

  31. Djavidani B, Sander M, Kreutz R, Zeh K, Bader M, Mellon SH et al. Chronic dexamethasone treatment suppresses hypertension development in the transgenic rat TGR(mREN2)27 J Hypertension 1995 13: 637–645

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by Pharmacia & Upjohn Corp. WS is especially grateful to Drs E Donovan-Wright and HA Robertson, Dalhousie University, Halifax, Canada, for the generous and joyful introduction into the DD RT-PCR world.

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Correspondence to W Sommer.

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Sommer, W., Arlinde, C., Caberlotto, L. et al. Differential expression of diacylglycerol kinase iota and L18A mRNAs in the brains of alcohol-preferring AA and alcohol-avoiding ANA rats. Mol Psychiatry 6, 103–108 (2001). https://doi.org/10.1038/sj.mp.4000823

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