MODELING THE DEPRESSIVE STATE IN RATS BY STEREOTAXIC INJECTION OF LIPOPOLYSACCHARIDE INTO THIRD VENTRICLE OF THE BRAIN

Abstract

Introduction: More than 4.4% of the world's population suffers from depression, which dramatically reduces both quality and life expectancy. For an accurate understanding of the links of pathogenesis and the possibility of correcting the depressive state, translational studies are widely used - in laboratory rodents. According to the modern concept of the inflammatory genesis of depression, the creation of animal models with nonspecific inflammation on the territory of the central nervous system is an urgent task. Purpose of the work: creation of a model of the depressive state in rats by injecting LPS into the third ventricle of the brain. Materials and methods: the study was carried out on female rats Wistar 280-300g. (n = 10), divided into 3 groups: 1 - with the introduction of LPS (n = 4), 2 - sham-operated (n = 3) and 3 - intact (n = 3). LPS was administered at a dose of 50 μg / animal in at volume of 4 μl in 15 minutes, according to the following stereotaxic coordinates: AP-0.8 ML-1.5 DV-3.5. Depression was assessed using the sucrose test and the behavior of animals in the open field tests, the elevated plus maze, the dark-light chamber, and the Porsolt test. Confirmation of the correct administration was carried out using MRI scanning (7 days) and postmortem on histological sections. Results: Animals treated with LPS showed a decrease in sucrose consumption, both compared to the sham-operated group and compared to the intact group. In behavioral tests, there was a decrease in locomotor activity in rats with the influence of LPS, but the differences between the group of sham-operated rats were insignificant. The experimental group had a sharp increase in the time of immobility in the Parsolt test (89.6 s VS 32.6 s VS 22.2 s) for the first, second and third groups, respectively. In the behavior of animals in the burrow chamber and in the open field, the presence of a neurological deficit in the experimental group was noted, consisting in a violation of gait in three out of four rats, in other groups this effect was not observed. When analyzing MRI images, the trace from the needle is traced exactly to the third ventricle. On a histological section in rats with neurological deficit, a demyelination area is visible (Fig. 1). Conclusion: The introduction of LPS into the cavity of the third ventricle causes depressive-like behavior in rats, a decrease in locomotor activity, but causes manifestations of neurological deficit as a result of local demyelination of the nervous tissue. The work was carried out within the framework of the state assignment of the Federal State Budgetary Educational Institution of Higher Education named after V.I. N.I. Pirogov for 2021–2023, state no. registration research work AAAA-A18-118051590108-1