DEVELOPMENT OF A TECHNIQUE FOR MODELING A DEPRESSIVE STATE IN RAT BY STEREOTAXIС INJECTION OF LIPOPOLYSACCHARIDE INTO THE HIPPOCAMPUS
Authors: D.I. Gonchar , D.N. Ljahman , V.I. Bogorodova , D.A. Borozdenko , N.M. Kiseleva , V.V. Negrebeckij 
Published: April 2022

Introduction: Currently, various mechanisms of the development of depression are known. At the beginning of the 21st century, a new era began in the study of the pathogenesis of this disease. It has been shown that the development of a depressive state is closely associated with neuroinflammation. As a result, it became necessary to develop methods for modeling depression, which will cause inflammation in a strictly defined area of the brain.
Purpose of the work: Creation of a model of the depressive state in rats by stereotaxic injection of LPS into the hippocampus.
Materials and Methods: Ten female Wistar rats were randomly divided into a control group (n = 3), an LPS-treated group (n = 4), and a sham-operated group (n = 3). LPS was administered at a dose of 30 μg / animal in a volume of 3 μL over 30 min, according to the following stereotaxic coordinates: AP: -3, ML: 2, DV: 3. Depression was assessed in psychopharmacological tests: hole-board test, open field, elevated plus maze, dark-light chamber, Porsolt forced swimming test, sucrose test. The formation of conditioned reflexes of passive avoidance was studied. To assess the localization of the injection, an MRI scan was performed on the 7th day. The result of LPS injection was analyzed on histological preparations.
Results: During testing of animals in the setting of a dark-light chamber and an elevated plus maze, it was found that the control and sham-operated groups did not have statistically significant differences. At the same time, the time spent by the rats in the light compartments increased in the experimental group. In the Porsolt forced swimming test, there are statistically significant differences in the time of immobilization of animals. Also, in the rats of the experimental group, the latent period of the onset of reversible actions increased. The study of the formation of a conditioned passive avoidance reflex can be considered not indicative, since two rats from the experimental group and one rat from the group of sham-operated animals did not enter the dark compartment of the installation and did not receive training. In the test for anhedonia, the rats of the experimental group showed a decrease in the consumption of sucrose as compared with the animals of the comparison groups. On histological preparations of the brain at the injection site, the formation of a glial-macrophage "shaft" (hematoxylin-eosin staining) is observed. When analyzing the MRI images, it was proved that the injection was made precisely in the hippocampus of rats.
Conclusion: Based on the results of the work, it can be concluded that this method of modeling depression is applicable in fundamental research, since the introduction of lipopolysaccharide into the hippocampus causes neuroinflammation in rats, and as a result, a depression state, and can be used to study the antidepressant activity of new drugs.

This work was carried out with the financial support of the Russian Science Foundation grant No. 21-73-20250.