The influence of long term housing in enriched environment on the social behavior of rats and the expression of genes associated with neuroinflammation

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Abstract

The aim of the work was to find out whether prolonged housing in an enriched environment is able to reduce the negative effects of early proinflammatory stress on the social behavior of adult male rats. On the 3rd and 5th postnatal days (PND), the rats were injected with either lipopolysaccharide at a dose of 50 mcg/kg (LPS group) or saline solution (SAL group). Starting from 30 PND and until the end of the experiments, one part of the rats lived in an enriched environment (EE), and the other in standard conditions (STD). Testing of pairs of rats in the social dominance tube test revealed a lower number of victories in the SAL and LPS groups when contained in the OS than in similar groups of rats under STD conditions. The dominant properties of males of the LPS group in SAL-LPS pairs weakened under the influence of EE. In the resident intruder test, the number of aggressive attacks, offensive uprights, sexual attacks, and the time of intruder persecution decreased in males of the LPS group when kept in the EE, while the number of attacks increased in rats of the SAL group, on the contrary. Analysis of cytokine gene expression in SAL rats, but not in the LPS group, showed an increase in the expression of anti-inflammatory cytokine TGF-beta1 mRNA in the dorsal hippocampus, amygdala and proinflammatory cytokine IL-1beta in the prefrontal cortex after housing in the EE. Thus, the housing in the EE had a beneficial effect on the behavior of the rats of the LPS group, reducing the dominant properties and aggressive behavior.

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About the authors

I. V. Pavlova

Institute of Higher Nervous Activity and Neurophysiology RAS

Author for correspondence.
Email: pavlovfml@mail.ru
Russian Federation, Moscow

N. D. Broshevitskaya

Institute of Higher Nervous Activity and Neurophysiology RAS

Email: pavlovfml@mail.ru
Russian Federation, Moscow

A. М. Shvadchenko

Institute of Higher Nervous Activity and Neurophysiology RAS

Email: pavlovfml@mail.ru
Russian Federation, Moscow

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2. Fig. 1. The effect of housing in an enriched environment on the behavior of rats in the social preference test. СТАНД – rats living in standard conditions, ОС – in an enriched environment. CO is a social object, НСО is a non–social object. ФИЗ – animals with the introduction of saline solution, ЛПС – with the introduction of lipopolysaccharide. * – differences between the СТАНД and ОС groups (p < 0.05), # – trend (0.05 < p < 0.1, post hoc Factorial ANOVA analysis). n is the number of rats in the ФИЗ/ЛПС groups.

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3. Fig. 2. The effect of housing rats in an enriched environment on social dominance in the tube test. Vertically, (a) is the percentage of wins and draws in pairs of ОС–СТАНД rats, (б) the average number of pushes, advances and retreats committed by rats in duels of animals kept in different conditions (ОС-СТАНД pairs), (в) the percentage of wins and draws in pairs of ФИЗ-ЛПС rats under similar housing conditions. * – differences between groups СТАНД and ОС (a, б) or ФИЗ and ЛПС (в) (p < 0.05, χ2, 2 x 2 Tables). The other symbols are as shown in Fig. 1.

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4. Fig. 3. The effect of housing rats in an enriched environment on the behavior in the resident-intruder test. * – statistically significant differences between the СТАНД and ОС groups (p < 0.05), # – trend (0.05 ≤ p < 0.1), + – differences between the ФИЗ and ЛПС groups (p < 0.05, Mann-Whitney U-test). The other symbols are as shown in Fig. 1.

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5. Fig. 4. The effect of housing in OC on the expression of proinflammatory (IL-1beta, TNF, IL-6) and anti-inflammatory cytokine (TGF-beta1) genes in the ФИЗ and ЛПС groups. Horizontally – brain structures (вмГПТ – ventromedial hypothalamus, дГПК – dorsal hippocampus, АМ – amygdala, дмПФК – dorsomedial prefrontal cortex). Vertically – the relative number of mRNAs. * – differences between СТАНД and ОС rats (p < 0.05), # – trend (0.05 ≤ p < 0.1), + – differences between ФИЗ and ЛПС groups under similar housing conditions (p < 0.05, Mann-Whitney U-test).

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