Model of ethanol withdrawal in rats

DOI: 10.29296/2618723X-2020-02-05

Kashkin V.1,2

1 Valdman Institute of Pharmacology, First Pavlov St. Petersburg State Medical University, 6-8, Lev Tolstoy St., Saint Petersburg, Russia, 197022;

2 Sechenov Institute of Evolutionary Physiology and Biochemistry, 44 Morisa Toreza St., St. Petersburg, 194223, Russia;

E-mail: [email protected]

Keywords: alcohol withdrawal hypertension rat
For citation:

Kashkin V.A. Model of ethanol withdrawal in rats . Laboratory Animals for Science. 2020; 2. https://doi.org/10.29296/2618723X-2020-02-05

Abstract

The aim of this study was to develop a simple and reproducible protocol for the formation of alcohol withdrawal syndrome in rats. Experimental modeling of alcohol withdrawal was carried out by forced intragastric administration of 25% ethanol in a daily dose of 5 g/kg during 14 days. The success of pathology formation was assessed using behavioral analysis based on the data of emotional, stereotypic, and motor components of the behavior of experimental animals in the “Open field” test, as well as the results of evaluating the severity of the generalized motor activation reaction (audiogenic startle response) in rats. Instrumental assessment methods included monitoring systolic blood pressure (SBP), heart rate, as well as the state of the enzymatic blood system and the activity of the lipid peroxidation caused by the abolition of chronic alcohol consumption in rats.

Manifestations of the alcohol withdrawal syndrome were accompanied by behavioral stress, which was associated with an increase in anxiety and an increase in the reaction of generalized motor activation after presentation of a short audiogenic stimulus (startle response), an increase in SBP by an average of 20 mmHg. Biochemical analysis of the enzymatic activity showed an increase in the concentration of creatinine and the activity of AST and LDH in blood plasma. The alcohol withdrawal was indicated by a decrease in the activity of enzymes of the antioxidant system, such as superoxide dismutase, glutathione peroxidase, and glutathione transferase, which are signs of the development of oxidative stress during the chronic exposure to alcohol.

Thus, the long forced administration of 25% ethanol allowed the formation of a pathology that was characterized by symptoms of withdrawal without lethal cases. The protocol includes the recommended evaluation methods that allow identifying the effectiveness of the tested drugs for the prevention and relief of manifestations of the alcohol withdrawal in the experiment.

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Acknowledgements. The study reported by the Research and manufacturing company «Home оf Pharmacy». I also express my appreciation to Faustova N.M., PhD, for conducting biochemical studies.

References

  1. O'Brien C. P., McLellan A. T. Myths about the treatment of addiction // Lancet. ‒ 1996. ‒ V. 347, No 8996. ‒ P. 237-240.
  2. Thompson W. L. Management of alcohol withdrawal syndromes // Arch.Intern.Med. ‒ 1978. ‒ V. 138, No 2. ‒ P. 278-283.
  3. Uzbay I. T., Usanmaz S. E., Tapanyigit E. E., Aynacioglu S., Akarsu E. S. Dopaminergic and serotonergic alterations in the rat brain during ethanol withdrawal: association with behavioral signs // Drug Alcohol Depend. ‒ 1998. ‒ V. 53, No 1. ‒ P. 39-47.
  4. Wetterling T., Weber B., Depfenhart M., Schneider B., Junghanns K. Development of a rating scale to predict the severity of alcohol withdrawal syndrome // Alcohol Alcohol. ‒ 2006. ‒ V. 41, No 6. ‒ P. 611-615.
  5. Hughes J. R. Alcohol withdrawal seizures // Epilepsy Behav. ‒ 2009. ‒ V. 15, No 2. ‒ P. 92-7. doi: 10.1016/j.yebeh.2009.02.037
  6. Di Gennaro C., Vescovi P. P., Barilli A. L., Giuffredi C., Delsignore R., Montanari A. Sodium sensitivity as a main determinant of blood pressure changes during early withdrawal in heavy alcoholics // Alcohol Clin.Exp.Res. ‒ 2002. ‒ V. 26, No 12. ‒ P. 1810-1815.
  7. Kashkin V. A., Zvartau E. E., Fedorova O. V., Bagrov Y. Y., Lakatta E. G., Bagrov A. Y. Endogenous bufadienolide mediates pressor response to ethanol withdrawal in rats // Eur Neuropsychopharmacol. ‒ 2008. ‒ V. 18, No 1. ‒ P. 74-7. doi: 10.1016/j.euroneuro.2007.05.006
  8. D’Souza El-Guindy N. B., Kovacs E. J., De Witte P., Spies C., Littleton J. M., De Villiers W. J. S., Lott A. J., Plackett T. P., Lanzke N., Meadows G. G. Laboratory Models Available to Study Alcohol-Induced Organ Damage and Immune Variations: Choosing the Appropriate Model // Alcoholism: Clinical and Experimental Research. ‒ 2010. ‒ V. 34, No 9. ‒ P. 1489-1511. doi: 10.1111/j.1530-0277.2010.01234.x
  9. Tiwari V., Kuhad A., Chopra K. Suppression of neuro-inflammatory signaling cascade by tocotrienol can prevent chronic alcohol-induced cognitive dysfunction in rats // Behav Brain Res. ‒ 2009. ‒ V. 203, No 2. ‒ P. 296-303. doi: 10.1016/j.bbr.2009.05.016
  10. Siech M., Heinrich P., Letko G. Development of acute pancreatitis in rats after single ethanol administration and induction of a pancreatic juice edema // Int J Pancreatol. ‒ 1991. ‒ V. 8, No 2. ‒ P. 169-75. doi: 10.1007/bf02924430
  11. Lieber C. S., Decarli L. M. Animal models of ethanol dependence and liver injury in rats and baboons // Fed Proc. ‒ 1976. ‒ V. 35, No 5. ‒ P. 1232-6.
  12. Bautista A. P., Spitzer J. J. Role of Kupffer cells in the ethanol-induced oxidative stress in the liver // Front Biosci. ‒ 1999. ‒ V. 4. ‒ P. D589-95. doi: 10.2741/bautista
  13. Руководство по наркологии, Т.1. / Иванец Н. Н. ‒ М.: МЕДПРАКТИКА-М, ‒2002. ‒ 443 c. [Guideline of Narcology, Vol.1. / Ivanets N. N. ‒ M.: MEDPRAKTIKA-M, ‒2002. ‒ 443 c.] (In Russ.)
  14. Goldstein D. B., Pal N. Alcohol dependence produced in mice by inhalation of ethanol: grading the withdrawal reaction // Science. ‒ 1971. ‒ V. 172, No 3980. ‒ P. 288-290. doi: 10.1126/science.172.3980.288
  15. Hölter S. M., Linthorst A. C. E., Reul J. M. H. M., Spanagel R. Withdrawal Symptoms in a Long-Term Model of Voluntary Alcohol Drinking in Wistar Rats // Pharmacology Biochemistry and Behavior. ‒ 2000. ‒ V. 66, No 1. ‒ P. 143-151. doi: 10.1016/S0091-3057(00)00196-9
  16. Dahchour A., De Witte P. Taurine blocks the glutamate increase in the nucleus accumbens microdialysate of ethanol-dependent rats // Pharmacol Biochem Behav. ‒ 2000. ‒ V. 65, No 2. ‒ P. 345-50. doi: 10.1016/s0091-3057(99)00197-5
  17. Majchrowicz E. Induction of physical dependence upon ethanol and the associated behavioral changes in rats // Psychopharmacologia. ‒ 1975. ‒ V. 43, No 3. ‒ P. 245-54. doi: 10.1007/bf00429258
  18. Spanagel R., Putzke J., Stefferl A., Schobitz B., Zieglgansberger W. Acamprosate and alcohol: II. Effects on alcohol withdrawal in the rat // Eur J Pharmacol. ‒ 1996. ‒ V. 305, No 1-3. ‒ P. 45-50. doi: 10.1016/0014-2999(96)00175-6
  19. Пошивалов В.П., Фармакоэтология: сб. статей. / Звартау Э. Э. ‒ СПб.: «Copy-Service», 1997. [Poshivalov V.P., Pharmacoetology: sb. statei. / Zvartau E. E. ‒ SPb.: «Copy-Service», 1997 (In Russ.)]
  20. Rassnick S., Koob G. F., Geyer M. A. Responding to acoustic startle during chronic ethanol intoxication and withdrawal // Psychopharmacology (Berl). ‒ 1992. ‒ V. 106, No 3. ‒ P. 351-8. doi: 10.1007/bf02245417
  21. Энзимопатии при алкоголизме / Чернобровкина T. B. ‒ Киев: Здоровье, 1992. ‒ 312 с. [Enzymopathies in alcoholism / Chernobrovkina T. B. ‒ Kiev: Zdorov'e, 1992. ‒ 312 p. (In Russ.)]
  22. Малинин М. Л., Тихомирова Е. И., Обух Л. Б., Кияшко В. В., Ласкавый В. Н. Половые различия по биохимическим поаказателям крови у разных видов лабораторных животных // Известия Саратовского университета. ‒ 2008. ‒ Т. 8, № 1. ‒ С. 52-54. [Malinin M. L., Tikhomirova E. I., Obukh L. B., Kiyashko V. V., Laskavyi V. N. Gender differences in biochemical blood parameters in different types of laboratory animals // Izvestiya Saratovskogo universiteta. ‒ 2008. ‒ T. 8, № 1. ‒ S. 52-54. (In Russ.)]
  23. Костюк В. А., Потапович А. И., Ковалева Ж. В. Простой и чувствительный метод определения активности супероксиддисмутазы, основанный на реакции окисления кверцетина // Вопросы медицинской химии. ‒ 1990. ‒ Т. 36, № 2. ‒ С. 88-91. [Kostyuk V. A., Potapovich A. I., Kovaleva Zh. V. A simple and sensitive method for determining the activity of superoxide dismutase, based on the oxidation reaction of quercetin // Voprosy meditsinskoi khimii. ‒ 1990. ‒ T. 36, № 2. ‒ P. 88-91 (In Russ.)]
  24. Современные проблемы биохимии. Методы исследований / Чиркин А. А. ‒ Минск: Высш. Школа, 2013. ‒ 491 с. [Modern problems of biochemistry. Research methods / Chirkin A. A. ‒ Minsk: Vyssh. Shkola, 2013. ‒ 491 p. (In Russ.)]
  25. Методы ветеринарной клинической лабораторной диагностики: Справочник / Кондрахин И. П. ‒ М: КолосС, 2004. ‒ 520 с. [Methods of Veterinary Clinical Laboratory Diagnostics: A Guide / Kondrakhin I. P. ‒ M: KoloSS, 2004. ‒ 520 p. (In Russ.)]
  26. Медицинские лабораторные технологии. Справочник / Карпищенко А. И. ‒ СПб: Интермедика, 2002. ‒ 600 с. [Medical laboratory technology. Directory / Karpishchenko A. I. ‒ SPb: Intermedika, 2002. ‒ 600 p. (In Russ.)]
  27. Grubbs F. E. Procedures for Detecting Outlying Observations in Samples // Technometrics. ‒ 1969. ‒ V. 11, No 1. ‒ P. 1-21. doi: 10.1080/00401706.1969.10490657
  28. Ord K. Outliers in statistical data // International Journal of Forecasting. ‒ 1996. ‒ V. 12, No 1. ‒ P. 175-176. doi: 10.1016/0169-2070(95)00625-7
  29. Peng F. C., Tang S. H., Huang M. C., Chen C. C., Kuo T. L., Yin S. J. Oxidative status in patients with alcohol dependence: a clinical study in Taiwan // J Toxicol Environ Health A. ‒ 2005. ‒ V. 68, No 17-18. ‒ P. 1497-509. doi: 10.1080/15287390590967432
  30. Huxtable R. J. Taurine in the central nervous system and the mammalian actions of taurine // Prog.Neurobiol. ‒ 1989. ‒ V. 32, No 6. ‒ P. 471-533.
  31. Сибирева О. Ф., Хитринская Е. Ю., Калюжина Е. В., Зибницкая Л. И., Ткалич Л. М., Бухарова Е. О., Калюжин В. В. Состояние антиоксидантного потенциала крови и свободнорадикальное окисление липидов у больных алкоголизмом, ассоциированным с поражением почек // Нефрология. ‒ 2009. ‒ Т. 13(1). ‒ С. 78-81. [Sibireva O. F., Khitrinskaya E. Yu., Kalyuzhina E. V., Zibnitskaya L. I., Tkalich L. M., Bukharova E. O., Kalyuzhin V. V. The state of blood antioxidant potential and free radical lipid oxidation in patients with alcoholism associated with kidney damage // Nefrologiya. ‒ 2009. ‒ T. 13(1). ‒ P. 78-81 (In Russ.)]
  32. Chopra K., Tiwari V. Alcoholic neuropathy: possible mechanisms and future treatment possibilities // Br.J.Clin.Pharmacol. ‒ 2012. ‒ V. 73, No 3. ‒ P. 348-362. doi: 10.1111/j.1365-2125.2011.04111.x

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