The Possibility of Using Wistar Rats as a Model Organism in Studying the Inflammation and Non-Predictable Stress on Anxiety and Sleep-Wake Cycles

Introduction. The “Double Hit” method represents a model of exposure to two damaging factors acting at different stages of ontogenesis. It is well established that stress may serve as a trigger for the development of central nervous system disorders, particularly when occurring against a background of altered levels of pro- and anti-inflammatory factors induced by early-life inflammation.

Materials and Methods. Wistar rats were used to model the effects of two damaging factors: neonatal inflammation induced by intraperitoneal administration of lipopolysaccharide on postnatal days (PND) 7 and 9 at a dose of 50 μg/kg, and repeated stress exposure during adolescence. Anxiety-like behavior was assessed twice: prior to stress exposure using the O-maze (PND 31) and after stress using the Elevated Plus Maze (PND 40). Between PND 36 and 39, a subset of animals was subjected to a subchronic unpredictable stress protocol. At the age of three months, male rats underwent surgical implantation of nichrome electrodes followed by continuous polysomnographic recording.

Results. Early postnatal inflammation did not affect anxiety levels or sleep architecture in rats. In contrast, exposure to subchronic unpredictable stress during the prepubertal period led to the development of hyperactivity and disrupted the duration of sleep–wake cycles.

Discussion. Laboratory rats (in particular, Wistar rats) were subjected to prolonged domestication and kept in controlled conditions for many generations, which led to a decrease in their adaptive potential. Thus, laboratory rats, like modern humans, exist in an artificially stabilized environment, which makes them more sensitive to external influences compared to their wild relatives.

Conclusion. Despite the inherently high biological plasticity of Rattus norvegicus, laboratory rat strains represent an adequate and informative model for studying processes relevant to the human population.

Ethics approval. The study was approved by the Bioethics Committee of Lomonosov Moscow State University (Protocol No. 194-zh, dated December 26, 2024) and conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS No. 123) and Directive 2010/63/EU of the European Parliament and of the Council.

Acknowledgments. The authors sincerely thank Vladimir M. Kovalzon for his assistance in organizing the experiments and for invaluable advice on data processing.

Contributions:
Kulpina A.A. — methodological development, experimental work;
Gerasimov A.A. — methodological development, experimental work;
Manchenko D.M. — literature review, manuscript writing;
Glazova N.Yu. — statistical analysis, manuscript writing;
Levitskaya N.G. — overall project coordination, manuscript writing.
All authors approved the final version of the manuscript and take responsibility for the integrity of all its parts.

Funding. This research was carried out within the framework of the state assignment to Lomonosov Moscow State University.

Conflict of interest. The authors declare no apparent or potential conflicts of interest related to the publication of this article.

Received: 07.07.2025 / Accepted: 20.08.2025 / Published: 10.09.2025

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