BEHAVIORAL REACTIONS OF RODENTS AFTER ADMINISTRATION OF THE 1,2,3-TRIAZOLO-1,4-BENZODIAZEPINES DERIVATIVES IN THE OPEN FIELD TEST

Authors

DOI:

https://doi.org/10.11603/2312-0967.2023.4.14297

Keywords:

triazolobenzodiazepines derivatives, “open field” test, spontaneous locomotor activity, grooming, mice

Abstract

The aim of the work. Study of the effect of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the behavioral reactions of rodents in the “open field” test.

Materials and Methods. Before using 1,2,3-triazolo-1,4-benzodiazepines under the code MA-252, MA-253, MA-254, MA-255 and MA-261 in in vivo experiments, the derivatives were triturated with lactose in a ratio of 1: 1000. Behavioral reactions of rodents were evaluated in the “open field” test, during which the number of crossed squares, rearings, exploratory nose-pokes, acts of defecation, urination and grooming were recorded.

Results and Discussion. The locomotor activity, which is characterized by the number of crossed squares, increased with the introduction of the MA-253 derivative in all investigated doses compared to the index in the control group and was not significantly different from the animals' group receiving gidazepam. The largest number of rearings, which is a manifestation of the exploratory activity of the animal under the test conditions, was observed in the experimental groups that received MA-253 and MA-255 derivatives in a dose of 1 mg/kg and the comparison drug gidazepam. Many of the studied groups observed an increase in the number of nose-pokes, but significant changes were only in the groups that received the MA-253 derivative and gidazepam at a dose of 1 mg/kg. The effect on the emotional component of the behavioral reactions of rodents has also been established.

Conclusions. It was found that the MA-253 derivative in a dose of 1 mg/kg produces the most significant changes, increasing locomotor and orientation-exploratory activity, while reducing the number of emotional manifestations in animals, which in terms of effect is similar to the reference drug gidazepam. Such mice behavior may indicate a reduction in the level of anxiety and psycho-emotional stress of animals, as well as the prospect of further studies of pharmacological activity.

Author Biographies

I. V. Botsula, National Pharmaceutical University of the Ministry of Health of Ukraine

postgraduate student of the Department of Clinical Pharmacology and Clinical Pharmacy

I.V. Kireyev, National Pharmaceutical University of the Ministry of Health of Ukraine

DSc (Medicine), professor, head of Department of Clinical Pharmacology and Clinical Pharmacy

O. M. Koshovyi, National Pharmaceutical University of the Ministry of Health of Ukraine

DSc (Pharmacy), professor of the Department of Pharmacognosy and Nutriciology

M. O. Mazur, State Scientific Institution "Institute for Single Crystals" NAS of Ukraine

Engineer of Department of Organic and Bioorganic Chemistry

V. A. Chebanov, State Scientific Institution "Institute for Single Crystals" NAS of Ukraine

DSc (Chemistry), Professor, Corresponding Member of NAS of Ukraine, First Deputy General Director

References

Harro J. Animals, anxiety, and anxiety disorders: How to measure anxiety in rodents and why. Behav Brain Res. 2018;352:81-93. https://doi:10.1016/j.bbr.2017.10.016.

Oberrauch S, Sigrist H, Sautter E, Gerster S, Bach DR, Pryce CR. Establishing operant conflict tests for the translational study of anxiety in mice. Psychopharmacology (Berl). 2019 Aug;236(8):2527-2541. doi: 10.1007/s00213-019-05315-y.

Prut L, Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. European journal of pharmacology. 2003;463(1-3):3–33. https://doi.org/10.1016/s0014-2999(03)01272-x.

Buccafusco JJ (Ed.). Methods of Behavior Analysis in Neuroscience. (2nd ed.). CRC Press/Taylor & Francis. 2009. https://doi.org/10.1201/noe1420052343.

Golovenko MY. The role of 1,4-benzodiazepine derivatives and related compounds in studying the morphofunctional organization of GABA neuroreceptors (literature review). Pharmacology and medicinal toxicology. 2020; 14(6):375-388.

Garakani A, Murrough JW, Freirem RC, Thom RP, Larkin K, Buono FD, Iosifescu DV. Pharmacotherapy of Anxiety Disorders: Current and Emerging Treatment Options. Front. Psychiatry. 2020;11:595584. doi: 10.3389/fpsyt.2020.595584.

Mehrhoff EA, Booher WC, Hutchinson J, Schumacher G, Borski C, Lowry CA, Hoeffer CA, Ehringer MA. Diazepam effects on anxiety-related defensive behavior of male and female high and low open-field activity inbred mouse strains. Physiol Behav. 2023 Nov 1;271:114343. doi: 10.1016/j.physbeh.2023.114343.

Belhassan A, Zaki H, Benlyas M, Lakhlifi T, Bouachrine M. Study of novel triazolo-benzodiazepine analogues as antidepressants targeting by molecular docking and ADMET properties prediction. Heliyon. 2019;5(9), e02446. https://doi.org/10.1016/j.heliyon.2019.e02446.

Amouzad Mahdirejei H, Peeri M, Azarbayjani MA, Masrour FF. Diazepam and exercise training combination synergistically reduces lipopolysaccharide-induced anxiety-like behavior and oxidative stress in the prefrontal cortex of mice. Neurotoxicology. 2023 Jul;97:101-108. doi: 10.1016/j.neuro.2023.06.004. Epub 2023 Jun 7. PMID: 37295748.

Groenink L., Verdouw P.M., Zhao Y. et al. Pharmacological modulation of conditioned fear in the fear-potentiated startle test: a systematic review and meta-analysis of animal studies. Psychopharmacology. 2023;240:2361–2401. https://doi.org/10.1007/s00213-022-06307-1

Botsula IV, Kireyev IV, Koshovyi OM, Chebanov VA. The influence of new 1,2,3-triazolo-1,4-benzodiazepine derivatives on the muscle tone of rodents. Current Issues in Pharmacy and Medicine: Science and Practice. 2023;16(3):217–222. https://doi.org/10.14739/2409-2932.2023.3.287999

Mazur MO; Zhelavskyi OS; Zviagin EM; Shishkina SV; Musatov VI; Kolosov MA; Shvets EH; Andryushchenko AY; Chebanov VA. Effective Microwave-Assisted Approach to 1,2,3-Triazolobenzodiazepinones via Tandem Ugi Reaction/Catalyst-Free Intramolecular Azide–Alkyne Cycloaddition. Beilstein J. Org. Chem. 2023;17(1):678–687. https://doi.org/10.3762/bjoc.17.57.

Council Directive 2010/63/EU of 22 September 2010 on the protection of animals used for scientific purposes. Official Journal of the European Communities. 2010;276:33–79.

Guide for the care and use of laboratory animals. Washington: The National Academies Press. 2011;246.

Stefanov OV. Preclinical studies of drugs. Avicenna: Kyiv, 2001.

Podolsky IM, Shtrygol' SY, Zubkov VO. The psycho- and neurotropic profiling of novel 3-(N-R,R'-aminomethyl)-2-methyl-1H-quinolin-4-ones in vivo. Saudi Pharm J. 2018; 26(1):107-114. doi:10.1016/j.jsps.2017.10.005

Starchenko G, Hrytsyk A, Raal A, Koshovyi О. Phytochemical profile and pharmacological activities of water and hydroethanolic dry extracts of Calluna vulgaris (L.) Hull. herb. Plants. 2020;9:751. https://doi.org/10.3390/plants9060751.

Koshovyi O, Raal A, Kireyev I, Tryshchuk N, Ilina T, Romanenko Y, Kovalenko S, Bunyatyan N. Phytochemical and Psychotropic Research of Motherwort (Leonurus cardiaca L.) Modified Dry Extracts. Plants. 2021;10: 230. https://doi.org/10.3390/plants10020230.

Choleris E, Thomas AW, Kavaliers M, Prato FS. A detailed ethological analysis of the mouse open field test: effects of diazepam, chlordiazepoxide and an extremely low frequency pulsed magnetic field. Neuroscience and biobehavioral reviews. 2001;25(3):235–260. https://doi.org/10.1016/s0149-7634(01)00011-2.

Kuniishi H, Ichisaka S, Yamamoto M, Ikubo N, Matsuda S, Futora E, Harada R, Ishihara K, Hata Y. Early deprivation increases high-leaning behavior, a novel anxiety-like behavior, in the open field test in rats. Neuroscience research. 2017;123:27–35. https://doi.org/10.1016/j.neures.2017.04.012.

Mukvych VV, Lyashenko VP, Lukashov SM. Age-related changes in the behavioral responses of male and female rats in the open field test. Bulletin of the Zaporizhian National University. Biological sciences. 2017;2:75–78.

Rosso M, Wirz R, Loretan AV, Sutter NA, Pereira da Cunha CT, Jaric I, Würbel H, Voelkl B. Reliability of common mouse behavioural tests of anxiety: A systematic review and meta-analysis on the effects of anxiolytics. Neuroscience and biobehavioral reviews. 2022;143:104928. https://doi.org/10.1016/j.neubiorev.2022.104928.

Tozyuk OY. Characteristics of emotional and behavioral reactions of rats under conditions of chronic immobilization stress against the background of the action of the 5-R-thio-tetrazolo (1,5-s) quinazoline derivative. Zaporozhye Medical Journal. 2013;5:57-59. http://nbuv.gov.ua/UJRN/Zmzh_2013_5_18.

Published

2023-11-30

How to Cite

Botsula, I. V., Kireyev, I., Koshovyi, O. M., Mazur, M. O., & Chebanov, V. A. (2023). BEHAVIORAL REACTIONS OF RODENTS AFTER ADMINISTRATION OF THE 1,2,3-TRIAZOLO-1,4-BENZODIAZEPINES DERIVATIVES IN THE OPEN FIELD TEST. Pharmaceutical Review Farmacevtičnij časopis, (4), 70–77. https://doi.org/10.11603/2312-0967.2023.4.14297

Issue

Section

Pharmacological researches of biologically active substances