Combined effect of chronic stress and chemical factor on anxietay in rats

Introduction. Chemical exposure can cause a wide range of adverse health effects depending on external and internal environmental conditions. Oxidative stress can enhance responses to psychoemotional stress, which leads to a deterioration in body’s adaptation to stressful conditions. In particular, when studying effect of paracetamol under stress, it is important to evaluate behavioral response indicators, since stress can significantly modify the body’s response to pharmacological agents.

Objective. To evaluate an effect of the combined exposure to chemical factor and chronic stress to behavioral response indicators in conditions of the subchronic experiment.

Materials and methods. Experiment was conducted on Wistar rats divided into 4 groups: control, chronic stress, paracetamol, combined exposure. Once a week, behavioral indicators of the groups were assessed using the "Board with holes", "Elevated plus maze", "Forced exploration of the open field", "Multifunctional cage for measuring general motor activity" cages. Hippocampal tissues for histological examination were fixed and subjected to a standard histological processing procedure.

Results. Results of "hole board" show a decrease in exploratory activity in experimental groups rats. A decrease in vertical activity in combined exposure group is also shown. In experimental groups, there were rarer and longer freezing episodes in open field in paracetamol group, as in combined exposure group, a decrease in motor activity due intoxication was observed, while in stress group a shown increase in motor activity is a marker of a high level of anxiety. Also some signs of increased level of anxiety are observed in combined exposure group, but there they are masked by motor activity decrease due to intoxication. Histological examination showed no pathological changes in brain tissue.

Limitations. Relatively small sample size, use of one animal species and one concentration of toxicant.

Conclusion. The changes observed in behavioral response indicators of combined exposure group revealed no significant increase in anxiety level.

Compliance with ethical standards. The study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (protocol No. 01-02 of 02/08/2024). Throughout the study, the animals were kept under standard conditions with 12 hours of artificial lighting during the day, a relatively constant level of humidity (30–70%) and an air temperature of 20–25 °C. Manipulations with all animals were carried out strictly in compliance with the rules prescribed in basic regulatory documents, including the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (Strasbourg, 1986) and the Declaration of Helsinki on the Humane Treatment of Animals.

Contribution:
Karimov D.D. – collection and processing of material, statistical processing, writing;
Gizatullina A.A. – concept and design of the study, collection and processing of material, statistical processing, editing;
Akhmadeev A.R., Yakupova T.G., Khmel A.O, Ryabova Yu.V., Valova Ya.V. – collection and processing of material;
Karimov D.O. – concept and design of the study, statistical processing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. Industry research program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing for 2021–2025 “Scientific substantiation of the national system for ensuring sanitary and epidemiological well-being, managing health risks and improving the quality of life.

Received: February 21, 2025 / Revised: April 14, 2025 / Accepted: June 26, 2025 / Published: March 13, 2026