Glucocorticosteroid-induced behavioral changes during endotoxinemia in rats

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Abstract

BACKGROUND: Experimental endotoxemia, based on the injection of lipopolysaccharide, is used to study systemic inflammation. Glucocorticosteroids, such as methylprednisolone and dexamethasone, play a key role in modulating inflammation. They affect inflammatory mediators and cellular components, penetrating the blood-brain barrier. However, the cerebral effects of glucocorticosteroids are not well studied. The assessment of behavioral changes induced by lipopolysaccharide and glucocorticosteroids using the “open field” test will help explore the neurobiological mechanisms of inflammation and stress.

AIM: Study of the effect of glucocorticosteroids on behavioral and physiological changes induced by experimental endotoxinemia in rats.

METHODS: Six groups of Wistar rats, 10 males in each group, were used in the experiment. The first group was injected once intraperitoneally with physiological solution, the second group was injected with lipopolysaccharide (1 mg/kg), the 3rd group was injected with i/p dexamethasone, 2 mg/kg; the 4th group was injected with i/p dexamethasone, 2 mg/kg, 2 h before lipopolysaccharide injection; the 5th group was injected with i/p methylprednisolone, 2 mg/kg; the 6th group was injected with i/p methylprednisolone, 2 mg/kg, 2 h before lipopolysaccharide injection. During the first 4 h of the experiment, deep body temperature of the rats was measured every 30 min and after 24 h to construct a temperature curve. At several time points, the behavior and locomotor activity of the rats were evaluated in the open-field test.

RESULTS: The results obtained demonstrate that lipopolysaccharide administration causes changes in behavioral patterns such as stance, minking, locomotion, act of grooming and frizzing. No differences were found in the effects of glucocorticosteroid depending on the drug. Application of glucocorticosteroid promotes restoration of motor activity of animals, elimination of negative effects of lipopolysaccharide.

CONCLUSION: The studied glucocorticosteroid drugs dexamethasone and methylprednisolone had comparable anti-inflammatory effect in terms of severity, caused normalization of body temperature and eliminated behavioral changes caused by lipopolysaccharide.

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About the authors

Elena Ya. Lebedeva

Peter the Great Saint Petersburg Polytechnic University

Author for correspondence.
Email: lena988902@yandex.ru
ORCID iD: 0009-0003-9034-2353

Postgraduate Student

Russian Federation, Saint Petersburg

Ekaterina S. Kukushkina

Peter the Great Saint Petersburg Polytechnic University

Email: Eskukushkina@mail.ru
ORCID iD: 0009-0008-2441-8889

Postgraduate Student

Russian Federation, Saint Petersburg

Tatiana V. Tyutunnik

Institute of Experimental Medicine

Email: t.tanjon11@yandex.ru
ORCID iD: 0000-0002-2427-9355

Research Assistant at the Pavlov Department of Physiology, Laboratory of Neurochemistry

Russian Federation, Saint Petersburg

Victoria A. Maystrenko

Institute of Experimental Medicine

Email: Sch_Viktoriya@mail.ru
ORCID iD: 0000-0001-7004-7873

Junior Researcher at the Pavlov Department of Physiology, Laboratory of Neurochemistry

Russian Federation, Saint Petersburg

References

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  2. Suleymanova AM, Kulichenko TV. Safety of application of short courses of glucocorticosteroids: literature review. Pharmateka. 2017;11(344):6–13. EDN: ZFVJEZ
  3. Severyukhin YS, Lalkovičová M, Utina DM, et al. Comparative analysis of behavioral reactions and morphological changes in the rat brain after exposure to ionizing radiation with different physical characteristics. Cell Mol Neurobiol. 2023;43(1):339–353. doi: 10.1007/s10571-021-01187-z
  4. Chudova AS, Alekhina NA, Gladysheva AO, et al. Determination of individual-typological features of behavior in Wistar rats in the open field test. Trends in the development of science and education. 2022;(88(1)):130–133. EDN: NHDQHI doi: 10.18411/trnio-08-2022-38
  5. Gevorkyan VS. Study of the impact of the same stress factors on the behavior of rats of different species and lines. Electronic scientific edition Almanac Space and Time. 2017;15(1):1–5. EDN: ZXYVFB
  6. Bobyntsev II, Korobova VN, Vorvul’ AO, et al. Correlation of heart rate variability and behavioural indicators in wistar rats. Humans and their health. 2023;26(4):72–87. EDN: KEYOHB doi: 10.21626/vestnik/2023-4/07
  7. Cherepovskaya NA, Zhunusov NS, Miller ES. Study of behavioral activity in the test “open field”. Scientific electronic journal Meridian. 2020;(4):75–77. (In Russ.) EDN: USBXDY

Supplementary files

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2. Fig. 1. Measurement of deep body temperature in rats endotoxemia experimental model. a, effect of lipopolysaccharide (LPS) and the study drug dexamethasone; b, effect of lipopolysaccharide and the study drug methylprednisolone. For statistical processing of the data, analysis of variance for independent samples followed by application of Tukey’s post-hoc criterion was used; * p < 0.05 compared with the control group; # p < 0.05 compared to the lipopolysaccharide group.

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3. Fig. 2. The influence of lipopolysaccharide (LPS) administration and investigational drugs on animal behavior in the Open Field test. a, number of supported stands before the study; b, number of supported struts after 48 h. Data are presented as mean ± error of the mean; analysis of variance for independent samples followed by Tukey’s post-hoc test; * p < 0.05 compared with the control group; # p < 0.05 compared with the lipopolysaccharide group.

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4. Fig. 3. The influence of lipopolysaccharide (LPS) administration and investigational drugs on animal behavior in the Open Field test at the 48-hour time point: a, number of upright posts; b, number of minks; c, number of acts of “sitting”; d, number of locomotion; e, number of frisking acts; f, number of grooming acts. Data are presented as mean ± error of the mean; analysis of variance for independent samples followed by Tukey’s post-hoc criterion; * p < 0.05 compared to control group; # p < 0.05 compared with the lipopolysaccharide group.

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5. Fig. 4. The influence of lipopolysaccharide (LPS) administration and investigational drugs on animal behavior in the Open Field test at the 48-hour time point: a, animal path; b, number of movements in place; c, number of sniffing. Data are presented as mean ± error of the mean; analysis of variance for independent samples followed by Tukey’s post-hoc test.

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