Evaluation of Noopept Effect on the Neurotransmitter Amino Acids in the Hippocampus in Alcohol Drinking Rats Using in Vivo Microdialysis

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10% (vol/vol) ETOH solution as the only source of fluid 24 h / 7 days per week (n = 5). Also we used intact rats of the same age which had no access to ethanol (n = 5). The excitatory and inhibitory amino acids in the extracellular space of the dorsal hippocampus region in freely moving intact and ETOH-exposed rats during prolonged alcohol deprivation were measured using the intracerebral microdialysis method followed by HPLC/ED. There were no significant differences in the level of neurotransmitter amino acids between ETOH-exposed and intact animals. For the first time, in vivo experiments the effect of Noopept (1.5 mg/kg, i.p.) on the level of excitatory amino acids (an increase in ASP by 2.38 times and GLU by 2.28 times) along with an increase in the level of the inhibitory amino acid GLI by 3.13 times only in intact rats was shown. Thus, in ETOH-exposed rats under the adaptive rearrangements in prolonged ethanol withdrawal, the neurochemical mechanisms of the hippocampus seem to be characterized by insensitivity to an acute Noopept administration. Animal neurochemical studies of changes in the mediator amino acids due to the long-term effect of alcohol on the CNS may be of practical importance for the development of optimal strategies and pharmacotherapy.

Full Text

Restricted Access

About the authors

V. S. Kudrin

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: lgkolik@mail.ru
Russian Federation, Moscow

V. G. Konkov

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: lgkolik@mail.ru
Russian Federation, Moscow

E. V. Shubenina

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Email: lgkolik@mail.ru
Russian Federation, Moscow

K. A. Kasabov

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies; I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lgkolik@mail.ru
Russian Federation, Moscow; Moscow

D. V. Sadovnik

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lgkolik@mail.ru
Russian Federation, Moscow

A. H. Khairetdinova

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lgkolik@mail.ru
Russian Federation, Moscow

A. E. Umriyukhin

I.M. Sechenov First Moscow State Medical University (Sechenov University)

Email: lgkolik@mail.ru
Russian Federation, Moscow

L. G. Kolik

Federal Research Center for Original and Prospective Biomedical and Pharmaceutical Technologies

Author for correspondence.
Email: lgkolik@mail.ru
Russian Federation, Moscow

References

  1. Zhao Y.N., Wang F., Fan Y.X., Ping G.F., Yang J.Y., Wu C.F. Behav // Brain Res. 2013. V. 236. P. 270—282.
  2. Mira R.G., Lira M., Tapia-Rojas C., Rebolledo D.L., Quintanilla R.A., Cerpa W. // Front. Behav. Neurosci. 2020. V. 13. Р. A.288.
  3. Kutlu M.G., Gould T J. // Learn Mem. 2016. V. 23. № 10. P. 515-33.
  4. Chefer V., Meis J., Wang G., Kuzmin A., Bakalkin G., Shippenberg T. // Addict. Biol. 2011. V. 16. P. 229—237.
  5. Sepulveda C., Bustos G., Gysling K., Seguel M., Labarca R. // Brain Res. 1995. V. 674. P. 104—106.
  6. Roberto M., Gilpin N.W., Siggins G.R. // Cold Spring Harb. Perspect. Med. 2012. V. 2. Р. A.012195.
  7. Littleton J. // Alcohol Health Res. 1998. V. 22. P. 13—24.
  8. Peris J., Eppler B., Hu M., Walker D.W., Hunter B.E., Mason K., Anderson K.J. // Alcohol Clin Exp Res. 1997 Sep. V. 21. № 6. P. 1047-52.
  9. Mistarz N., Andersen K., Nielsen A.S., Goudriaan A.E., Michel T.M., Skøt L., Nielsen D.G., Mellentin A.I. // Neurosci Biobehav Rev. 2021 Jun. V. 125. P. 608—626.
  10. Островская Р.У., Гудашева Т.А. // Экспериментальная и клиническая фармакология. 2021. Т. 84. № 2. С. 41—52.
  11. Коньков В.Г., Кудрин В.С., Наркевич В.Б., Колик Л.Г. // Нейрохимия. 2022. Т. 39. № 2. С. 160—167.
  12. Колик Л.Г., Коньков В.Г., Сорокина А.В., Мирошкина И.А., Касабов К.А., Кудрин В.С., Дурнев А.Д. // Молекулярная медицина. 2022. Т. 20. № 6. С. 56—64.
  13. Надорова А.В., Колик Л.Г., Клодт П.М., Наркевич В.Б., Наплёкова П.Л., Козловская М.М., Кудрин В.С. // Нейрохимия. 2014. Т. 31. № 2. С. 147.
  14. Parent M., Bush D., Rauw G., Master S., Vaccarino F., Baker G. // Methods. 2001. V. 23. № 1. P. 11—20.
  15. Paxinos G., Watson C. // San Diego, CA: Academic Press, 1998.
  16. De Witte P. // Addict Behav. 2004. V. № 7. P. 1325-39.
  17. Ward R.J., Colivicchi M.A., Allen R., Schol F., Lallemand F., de Witte P., Ballini C., Corte L.D., Dexter D. // J. Neurochem. 2009. V. 111. P. 1119—1128.
  18. Hermann D., Weber-Fahr W., Sartorius A., Hoerst M., Frischknecht U., Tunc-Skarka N., Perreau-Lenz S., Hansson A.C., Krumm B., Kiefer F., Spanagel R., Mann K., Ende G., Sommer W.H. // Biol. Psychiatry. 2012. V. 71. P. 1015—1021.
  19. Dahchour A., & De Witte P. // Clinical and Experimental Research. 1998. V. 22 (A109). 175.
  20. Поваров И.С., Кондратенко Р.В., Деревягин В.И., Островская Р.У., Скребицкий В.Г. // Бюллетень экспериментальной биологии и медицины. 2014. Т. 158. № 9. С. 336—338.
  21. Vorobyov V., Kaptsov V., Kovalev G., Sengpiel F. // Brain Res Bull. 2011. May. V. 30, № 85(3-4). P. 123-32.
  22. Firstova Iu.Iu., Vasil’eva E.V., Kovalev G.I. // Eksp Klin Farmakol. 2011. V. 74. № 1. P. 6—10.
  23. Kovalev G.I., Kondrakhin E.A., Salimov R.M., Neznamov G.G. // Eksp Klin Farmakol. 2014. № 77(12). Р. 3—9.
  24. Nalini K., Karanth K.S., Rao A., Aroor A.R. // Pharmacol Biochem Behav. 1992. V. 42. № 4. P. 859-64.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download
2. Fig. 1. Design of the experiment.

Download (115KB)
Indexing metadata
3. Fig. 2. The layout of the microdialysis probe in the dorsal hippocampus (a) and a photo of a section of the rat brain (b). The arrow indicates the place of origin and the direction of the trace channel of the microdialysis probe.

Download (283KB)
Indexing metadata
4. Fig. 3. The effect of a single systemic administration of noopept on the content of aspartate (ASP) in the hippocampus of mongrel rats. *p < 0.05 compared to the level at initial rest; #p < 0.05 compared to intact rats, according to the ANOVA planned comparison analysis followed by multiple Newman—Keils analysis.

Download (89KB)
Indexing metadata
5. Fig. 4. The effect of a single systemic administration of noopept on the content of glutamate (GLU) in the hippocampus of mongrel rats. *p < 0.05 compared to the level at initial rest, according to the ANOVA planned comparison analysis followed by multiple Newman—Keils analysis.

Download (84KB)
Indexing metadata
6. Fig. 5. The effect of noopept with a single systemic administration on the content of glycine (GLI) in the hippocampus of mongrel rats. *p < 0.05 compared to the level at initial rest; #p < 0.05 compared to intact rats, according to the ANOVA planned comparison analysis followed by multiple Newman—Keils analysis.

Download (88KB)
Indexing metadata
7. Fig. 6. The effect of noopept with a single systemic administration on the content of taurine (TAU) in the hippocampus in mongrel rats.

Download (86KB)
Indexing metadata
8. Fig. 7. The effect of noopept with a single systemic administration on the content of GABA in the hippocampus in mongrel rats.

Download (91KB)
Indexing metadata

Copyright (c) 2024 Russian Academy of Sciences