Physiological aspects of rat activity, their anxiety and memory after administration of full gabaa-receptor complex agonist propoxazepam

Authors

  • Mykola Golovenko A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080, Ukraine https://orcid.org/0000-0003-1485-128X
  • Igor Belenichev Zaporizhia State Medical University Maiakovskoho ave., 26, Zaporizhia, Ukraine, 69035, Ukraine https://orcid.org/0000-0003-1273-5314
  • Vitalii Larionov A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080, Ukraine https://orcid.org/0000-0003-2678-4264
  • Anatoliy Reder “INTERCHEM” SLC Liustdorfska doroha str., 86, Odessa, Ukraine, 65080 A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080, Ukraine https://orcid.org/0000-0002-1801-8378
  • Andronati Serhiy A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080, Ukraine https://orcid.org/0000-0001-8451-6327

DOI:

https://doi.org/10.15587/2519-8025.2020.207368

Keywords:

propoxazepam, locomotor and exploratory activity, reference and working memory

Abstract

The action of 7-bromo-5 (o-chlorophenyl) -3-propoxy-1,2-dihydro-3H-1,4-benzodiazepin-2-one (propoxazepam) with prolonged administration in various doses on behavioural reactions, anxiety and the memory of rats, as well as their muscle tone was estimated, which is important paying attention to its main (anticonvulsant and analgesic) pharmacological effects.

The aim of the study was a comparative assessment of the severity and duration of propoxazepam effect after its administration to rats at doses of 2, 5 and 10 mg/kg (10 days) on higher functions of the central nervous system according to indicators such as motor and exploratory activity, as well as reference and working memory .

Materials and methods. The study was conducted on 40 Wistar rats weighing 220-290 g. The psychophysiological state of the animals was evaluated using the "open field" test, the formation of spatial working and long-term memory in a radial eight-arm maze, muscle relaxation, imbalance and movements coordination - using the "rotating rod" method. Statistical processing was performed in Microsoft Excel 2016 with AtteStat 12.

The results of the study. When comparing the test results of the "open field", "radial labyrinth" and "rotarod" in groups of animals that were administered different doses of the compound, it was found that, in general, these parameters at doses of 2 mg/kg and 5 mg/kg statistically significantly different (increase) from control values, but are similar. At a dose of 10 mg/kg, most of the parameters (except for the rotarod test) for these animals were characterized by a downward trend.

Conclusions. The administration of the drug in doses of 2, 5 and 10 mg/kg leads to a decrease in anxious behaviour of animals, which is also accompanied by a pronounced dose-dependent negative effect on the endurance, coordination and memory of animals. The administration of the drug at a dose of 10 mg/kg impaired the learning ability of animals and reduced memory function. This should be considered in clinical studies of the compound

Author Biographies

Mykola Golovenko, A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080

Doctor of Biological Sciences, Professor, Chief Researcher, Academician of National Academy of Medical Sciences of Ukraine

Laboratory of Physico-Chemical Pharmacology

Igor Belenichev, Zaporizhia State Medical University Maiakovskoho ave., 26, Zaporizhia, Ukraine, 69035

Doctor of Biological Sciences, Professor, Head of Department

Department of Pharmacology and Medical Prescriptions

Vitalii Larionov, A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080

Doctor of Biological Sciences, Head of Laboratory

Laboratory of Physical-Chemical Pharmacology

Anatoliy Reder, “INTERCHEM” SLC Liustdorfska doroha str., 86, Odessa, Ukraine, 65080 A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080

PhD, General Director

Senior Researcher

Andronati Serhiy, A. V. Bogatsky Physical-Chemical Institute of National Academy of Sciences of Ukraine Liustdorfska doroha str., 86, Odessa, Ukraine, 65080

Doctor of Chemical Sciences, Professor, Head of Department, Academician of National Academy of Sciences of Ukraine

Department of Medicinal Chemistry

References

  1. Mamylina, N. V., Pavlova, V. I. (2013). Fiziologicheskie aspekty povedencheskoi aktivnosti zhivotnykh v usloviiakh emocionalnogo stressa. Cheliabinsk: «Cicero», 298.
  2. Golovenko, N. Y., Larionov, V. B., Reder, A. S., Valivodz’, I. P. (2017). An effector analysis of the interaction of propoxazepam with antagonists of GABA and glycine receptors. Neurochemical Journal, 11 (4), 302–308. doi: http://doi.org/10.1134/s1819712417040043
  3. Golovenko, N. Ya., Voloshchuk, N. I., Andronati, S. A., Taran, I. V., Reder, A. S., Pashynska, O. S., Larionov, V. B. (2018). Antinociception induced by a novel benzodiazepine receptor agonist and bradykinin receptor antagonist in rodent acute and chronic pain models. European Journal of Biomedical and Pharmaceutical Sciences, 5 (12), 79–88.
  4. Golovenko, N. Y., Kabanova, T. A., Andronati, S. A., Halimova, O. I., Larionov, V. B., Reder, A. S. (2020). Anti-inflammatory effects of propoxazepam on different models of inflammation. International Journal of Medicine and Medical Research, 5 (2), 105–112. doi: http://doi.org/10.11603/ijmmr.2413-6077.2019.2.10900
  5. Voloschuk, N. І., Reder, A. S., Golovenko, M. Ya., Taran, І. V., Pashinska, O. S. (2017). Farmakologіchniy analіz neyrohіmіchnih antinotsitseptivnih mehanіzmіv dіi propoksazepamu. Farmakologіya ta lіkarska toksikologіya, 1 (53), 3–11.
  6. Golovenko, M. Y., Larionov, V. B., Reder, A. S., Andronati, S. A., Valivodz’, I. P., Yurpalova, T. O. (2018). Pharmacodynamics of Interaction between Propoxazepam and a GABA-Benzodiazepine Receptor-Ionofor Complex. Neurophysiology, 50 (1), 2–10. doi: http://doi.org/10.1007/s11062-018-9711-9
  7. Golovenko, N. Y., Kovalenko, V. N., Larionov, V. B., Reder, А. S. (2020). Dose and time-dependent acute and subchronic oral toxicity study of propoxazepam in mice and rats. International Journal of Pharmacology and Toxicology, 8 (1), 1. doi: http://doi.org/10.14419/ijpt.v8i1.29531
  8. Organisation for Economic Cooperation and Development (2008). OECD Guideline for Testing of Chemicals (TG 407). Repeated Dose 28-Day Oral Toxicity Study in Rodents. OECD/OEDC.
  9. Voloshchuk, N. І., Тaran, І. V., Reder, А. S., Golovenko, M. Y. (2018). Experimental study of ulcerogenic action of propoxazepam. Reports of Vinnytsia National Medical University, 22 (1), 6–9. doi: http://doi.org/10.31393/reports-vnmedical-2018-22(1)-01
  10. Golovenko, M. Ya., Larionov, V. B., Reder, A. S. (2020). Investigation of safety profile of propoxazepam by salmonella/mocrosome test, Information, its impact on social and technical processes. SH SCW “NEW ROUTE”. Haifa, 162–165.
  11. Andronaty, S. A., Voronyna, T. A., Holovenko, N. Ya. (1992). Hydazepam. Kyiv: Naukova dumka, 196.
  12. Larionov, V. B., Holovenko, M. Ya., Valivodz, I. P., Reder, A. S. (2020). Psykhotropni vlastyvosti pokhidnoho 1,4-benzodiazepinu, potentsiinoho antykonvulsanta ta analhetyka iz polimodalnym mekhanizmom dii. Medychna nauka ta praktyka na suchasnomu istorychnomu etapi. Kyiv, 129–133.
  13. Volokhova, H. A., Stoianov, A. N., Tokman, E. P. (2009). Vlyianye solkoseryla na kohnytyvnie funktsyy pry yshemycheskom ynsulte. Liky Ukrainy, 4 (130), 110–114.
  14. Nadel, L., Hardt, O. (2010). Update on Memory Systems and Processes. Neuropsychopharmacology, 36 (1), 251–273. doi: http://doi.org/10.1038/npp.2010.169
  15. Whishaw, I. Q., Li, K., Whishaw, P. A., Gorny, B., Metz, G. A. (2008). Use of Rotorod as a Method for the Qualitative Analysis of Walking in Rat. Journal of Visualized Experiments, 22. doi: http://doi.org/10.3791/1030
  16. Perez-Leighton, C. E., Boland, K., Billington, C. J., Kotz, C. M. (2013). High and low activity rats: Elevated intrinsic physical activity drives resistance to diet-induced obesity in non-bred rats. Obesity, 21 (2), 353–360. doi: http://doi.org/10.1002/oby.20045
  17. West, C. H. K., Boss-Williams, K. A., Weiss, J. M. (1998). Motor activation by amphetamine infusion into nucleus accumbens core and shell subregions of rats differentially sensitive to dopaminergic drugs. Behavioural Brain Research, 98 (1), 155–165. doi: http://doi.org/10.1016/s0166-4328(98)00064-3
  18. Seibenhener, M. L., Wooten, M. C. (2015). Use of the Open Field Maze to Measure Locomotor and Anxiety-like Behavior in Mice. Journal of Visualized Experiments, 96, 524–534. doi: http://doi.org/10.3791/52434
  19. Belenichev, I., Burlaka, B., Puzyrenko, A., Ryzhenko, O., Kurochkin, M., Yusuf, J. (2019). Management of amnestic and behavioral disorders after ketamine anesthesia. Georgian Medical News, 9 (294), 141–145.
  20. Rex, A. (1996). “Anxiolytic” action of diazepam and abecarnil in a modified open field test. Pharmacology Biochemistry and Behavior, 53 (4), 1005–1011. doi: http://doi.org/10.1016/0091-3057(95)02121-3
  21. Seredenin, S. B., Blednov, Yu. A., Badyshtov, B. A., Gordey, M. L., Nagovitsina, Ya. (1990). Pharmacogenetic analysis of mechanisms of emotional stress: effects of benzodiazepines. Annali dell'Istituto Superiore di Sanità, 26 (1), 81–87.
  22. King, D. J. (1992). Benzodiazepines, amnesia and sedation: Theoretical and clinical issues and controversies. Human Psychopharmacology: Clinical and Experimental, 7 (2), 79–87. doi: http://doi.org/10.1002/hup.470070202

Downloads

Published

2020-04-30

How to Cite

Golovenko, M., Belenichev, I., Larionov, V., Reder, A., & Serhiy, A. (2020). Physiological aspects of rat activity, their anxiety and memory after administration of full gabaa-receptor complex agonist propoxazepam. ScienceRise: Biological Science, (2 (23), 42–48. https://doi.org/10.15587/2519-8025.2020.207368

Issue

No. 2 (23) (2020)

Section

Biological Sciences

License

Copyright (c) 2020 Mykola Golovenko, Igor Belenichev, Vitalii Larionov, Anatoliy Reder, Andronati Serhiy

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Our journal abides by the Creative Commons CC BY copyright rights and permissions for open access journals.

Authors, who are published in this journal, agree to the following conditions:

1. The authors reserve the right to authorship of the work and pass the first publication right of this work to the journal under the terms of a Creative Commons CC BY, which allows others to freely distribute the published research with the obligatory reference to the authors of the original work and the first publication of the work in this journal.

 2. The authors have the right to conclude separate supplement agreements that relate to non-exclusive work distribution in the form in which it has been published by the journal (for example, to upload the work to the online storage of the journal or publish it as part of a monograph), provided that the reference to the first publication of the work in this journal is included.