To study the dynamics of behavioral changes in rats under chronic stress and the use of paracetamol

Evaluation of rat behavior in experimental studies is important for understanding neurophysiological and psychopharmacological processes. The aim of this study is to investigate the effect of paracetamol on the behavioral responses of laboratory rats under chronic stress. Four groups of white outbred rats (N=48) were formed within the framework of the study. For statistical analysis of the data, specialized IBM SPSS Statistics version 21 software was used. The normality of distribution was checked using the Kolmogorov-Smirnov criterion. The data were then evaluated using one-way analysis of variance (ANOVA), with Tukey and Tamhane criteria used for multiple comparisons. The focus is on assessing changes in the cognitive and emotional spheres of animal behavior, as well as analyzing the possible neuroprotective properties of paracetamol under long-term stress exposure. This article describes changes in the behavioral responses of animals from different groups to objectively assess the effect of the drug on the levels of anxiety, depression, aggression and cognitive functions in rats under chronic stress. The behavior of rats on a board with holes, in a cage for measuring activity, in the Open Field and Elevated Plus Maze tests during a four-week study against the background of taking an aqueous solution of paracetamol is described. The results of this study confirm the hypothesis that the combination of stress and paracetamol intake has a significant effect on the behavioral activity of laboratory rats. This is manifested in a decrease in vertical and horizontal activity, changes in behavior in the elevated plus maze and a decrease in mobility in the open field. The obtained data can serve as a basis for further studies of the mechanisms of interaction between stress and pharmacological drugs on the central nervous system of animals.

1. Gorshkov, A.N. Morphological aspects of nephrotoxic action of nonsteroidal antiinflammatory drugs / A.N. Gorshkov, I.V. Marusov, O.D. Yagmurov et al. // Nephrologiya. — 2013. — Vol. 17, No. 1. — pp. 73–77. — DOI 10.24884/1561-6274-2013-17-1-73-77. (In Russ.)

2. Krishen', K.L. Experimental study of pharmacological safety of medicines used for fever reduction in children / K.L. Krishen', A.E. Moskov, M.N. Dem'yanovskiy et al. // Bezopasnost' i risk farmakoterapii. — 2020. — Vol. 8, No. 3. — pp. 151–159. — DOI 10.30895/2312-7821-2020-8-3-151-159. (In Russ.)

3. Vlasova, Yu.A. Study of neurotoxicity of paracetamol and its metabolite NAPQI (brief report) / Yu.A. Vlasova, N.E. Golovanova, Ch.R. Beishbebaeva et al. // Laboratornye zhivotnye dlya nauchnykh issledovaniy. — 2021. — No. 4. — DOI 10.29296/2618723X-2021-04-09. (In Russ.)

4. Bai, T. Construction and evaluation of a rat model of postpartum fatigue / T. Bai, F. Wu, S. Yan et al. // Gynecol Obstet Invest. — 2021. — Vol. 86, No. 4. — pp. 370–378. — DOI 10.1159/000517997.

5. Carola, V. Evaluation of the elevated plus -maze and open-field tests for assessing anxiety-related behaviors in inbred mice / V. Carola, F. D'Olimpio, E. Brunamonti et al. // Behav Brain Res. — 2002. — Vol. 134, Nos. 1–2. — pp. 49–57. — DOI 10.1016/S0166-4328(01)00452-1.

6. Mineshima, H. Comparative study on detectability of learning and memory disorders between two common water maze tests in juvenile rat toxicity studies using an isoflurane-inhaled rat model / H. Mineshima, H. Kimoto, M. Hitomi et al. // Congenit Anom (Kyoto). — 2022. — Vol. 62, No. 3. — pp. 96–104. — DOI 10.1111/cga.12460.

7. Brito, R.C. Static magnetic field blocks alprazolam-induced behavior of Wistar rats in the elevated plus-maze test / R.C. Brito, T. Olivato, T.T. Kitabatake et al. // Neurosci Lett. — 2023. — Vol. 794. — Art. no. 137013. — DOI 10.1016/j.neulet.2022.137013.

8. Matisz, C.E. Chronic unpredictable stress shifts rat behavior from exploration to exploitation / C.E. Matisz, C.A. Badenhorst, A.J. Gruber // Stress. — 2021. — Vol. 24, No. 5. — pp. 635–644. — DOI 10.1080/10253890.2021.1883323.

9. Molina, P. Restraint or immobilization: A comparison of methodologies for restricting free movement in rodents and their potential impact on physiology and behavior / P. Molina, R. Andero, A. Armario // Neurosci Biobehav Rev. — 2023. — Vol. 151. — Art. no. 105224. — DOI 10.1016/j.neubiorev.2023.105224.

10. Woo, E. Chronic stress weakens connectivity in the prefrontal cortex: Architectural and molecular changes / E. Woo, L.H. Sansing, A.F.T. Arnsten et al. // Chronic Stress (Thousand Oaks). — 2021. — Vol. 5. — Art. no. 24705470211029254. — DOI 10.1177/24705470211029254.

11. Armario, A. Focusing attention on biological markers of acute stressor intensity: Empirical evidence and limitations / A. Armario, J. Labad, R. Nadal // Neurosci Biobehav Rev. — 2020. — Vol. 111. — pp. 95– 103. — DOI 10.1016/j.neubiorev.2020.02.001.

12. Himanshu. A review of behavioral tests to evaluate different types of anxiety and anti-anxiety effects / Himanshu, Dharmila, D. Sarkar, Nutan // Clin Psychopharmacol Neurosci. — 2020. — Vol. 18, No. 3. — pp. 341–351. — DOI 10.9758/cpn.2020.18.3.341.

13. Bzykow, O. Use of various behavioral models when studying the reaction of rats under exposure to negative air ions / O. Bzykow, M. Marzoeva, Z. Khabaev et al. // Sibirskiy zhurnal nauk o zhizni i sel'skom khozyaistve. — 2022. — Vol. 14, No. 6. — pp. 92–106. — DOI 10.12731/2658-6649-2022-14-6-92-106. (In Russ.)

14. Loseva, E.V. Behavior of rats in anxiety tests after short-term intranasal administration of single-walled carbon nanotubes at low doses / E.V. Loseva, N.A. Loginova, L.I. Russu et al. // Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. — 2022. — Vol. 108, No. 11. — pp. 1525– 1541. (In Russ.)

15. Fedosova, E.A. Effect of methylenriched maternal diet on dopaminergic neuron number in ventral tegmental area of adult offspring brain in WAG/Rij line rats / E.A. Fedosova, N.A. Loginova, K.Yu. Sarkisova // Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. — 2023. — Vol. 109, No. 7. — pp. 902–920. (In Russ.)

16. Stepanichev, M.Yu. Chronic stress caused by nesting material deficiency during early postnatal period affects male rat behavior and stress reactivity / M.Yu. Stepanichev, O.A. Nedogreeva, M.A. Klimanova et al. // Zhurnal vysshey nervnoy deyatel'nosti imeni I.P. Pavlova. — 2021. — Vol. 71, No. 3. — pp. 370–376. (In Russ.)