Analysis of correlations between behavioral parameters in the elevated plus maze and the levels of interleukin-1beta in blood plasma in rats

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Abstract

Peripheral cytokines may influence psychoemotional behavior, but the role of interleukin-1beta (IL-1beta) in altering anxiety and motor activity in response to inflammatory activation remains unclear. To clarify this issue, correlations between behavioral parameters in the elevated plus maze (EPM) test and plasma levels of IL-1beta after administration of the proinflammatory stimulus lipopolysaccharide (LPS) in different modes were analyzed in adult male rats. LPS in doses of 0.5 or 5 mg/kg, as well as physiological solution (control), were administered to rats intraperitoneally. The most pronounced behavioral effect 24 hours after a single injection was an endotoxin dose-dependent inhibition of the animals’ motor activity. After a dose of 5 mg/kg, increased anxious behavior was also noted every other day. The behavioral changes caused by the high dose of endotoxin were completely normalized after a week. The behavior of the animals one day after the end of repeated injections of LPS at a lower dose for a week (0.5 mg/kg; once every two days) also did not differ from the control. The inhibition of motor activity after LPS could be due to an increase in the level of IL-1beta in the blood plasma, as indicated by the identified significant negative correlations between IL-1beta and the corresponding behavioral parameters. No significant correlation was found between the peripheral level of IL-1beta and such a classic indicator of anxiety as the percentage of entries into the open arms of the maze. In general, the obtained results allow us to conclude that IL-1beta is an undoubted participant in the mechanism of the transient inhibitory effect of LPS on motor activity.

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N. P. Komysheva

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Author for correspondence.
Email: agarina@bionet.nsc.ru
Russian Federation, Novosibirsk

G. T. Shishkina

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: agarina@bionet.nsc.ru
Russian Federation, Novosibirsk

A. I. Mukhamadeeva

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: agarina@bionet.nsc.ru
Russian Federation, Novosibirsk

N. N. Dygalo

Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences

Email: agarina@bionet.nsc.ru
Russian Federation, Novosibirsk

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2. Fig. 1. Changes in the parameters of anxiety behavior of adult rats in the PCL test 1 and 7 days after a single intraperitoneal injection of LPS: (a) percentage of entries into open arms (Open arms entries, %); (b) number of peeks out of the open arms (Head-dips, n); (c) percentage of time spent in the central area (Center area time, %). * – p < 0.05 compared to animals 24 hours after the injection of saline; # – p < 0.05 compared to animals 24 hours after the injection of LPS at a dose of 0.5 mg/kg.

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3. Fig. 2. Changes in the parameters of motor activity of adult rats in the PCL test 1 and 7 days after a single intraperitoneal administration of LPS: (a) – total number of entries into open and closed arms (Total arms entries, n); (b) – number of rearings (Rears, n); (c) – distance traveled in closed arms (Closed arms distance, cm); (d) – total distance traveled in open and closed arms (Total distance, cm). * – p < 0.05 compared to animals 24 hours after administration of saline; # – p < 0.05 compared to animals 24 hours after administration of LPS at a dose of 0.5 mg/kg; & – p < 0.05 compared to animals 24 hours after administration of LPS at a dose of 5 mg/kg.

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4. Fig. 3. Changes in the level of IL-1beta in the blood plasma of rats 1 and 7 days after a single intraperitoneal injection of LPS. * – p < 0.05 compared to animals 24 hours after the administration of saline; & – p < 0.05 compared to animals 24 hours after the administration of LPS at a dose of 5 mg/kg.

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5. Fig. 4. Correlations between IL-1beta levels in blood plasma and behavioral parameters in the PCL test one day after LPS administration: (a) – number of rearings; (b) – distance traveled in closed arms; (c) – total distance traveled in open and closed arms; (d) – percentage of entries into open arms.

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