EARLY STRESS OF MATERNAL DEPRIVATION AFFECTS THE EXPRESSION OF OX1R OREXIN IN THE LIMBIC SYSTEM OF THE BRAIN AND CONTRIBUTES TO THE DEVELOPMENT OF ANXIETY-DEPRESSIVE SYMPTOMS IN RATS.

Abstract

BACKGROUND. Depressive states are becoming an increasingly common mental disorder, as well as a serious social problem that places a heavy economic burden on society. More and more data from preclinical and clinical studies indicate that orexins (neuropeptides, also known as hypocretins) and their receptors are involved in the pathogenesis of depression. The orexinergic system regulates functions that are disrupted in depressive states, such as sleep, reward system, eating behavior, stress response and monoaminergic regulation. However, the exact role of orexins in behavioral and neurophysiological disorders observed in depression is still unclear. AIM. To study the effect of early postnatal stress on the expression of OX1R orexin in the limbic system of the brain and the development of anxiety-depressive symptoms in rats. MATERIALS AND METHODS. In the work, maternal deprivation was used as a model of early postnatal stress (from the 2nd to the 12th postpartum day). Two experimental groups were formed: control (n = 20); "maternal deprivation" (n = 20). On the 90th day of life, the influence of early postnatal stress on the development of anxiety-depressive symptoms in rats in adulthood was analyzed using a package of behavioral tests. Behavior analysis was performed using the following tests: raised cruciform maze, forced swimming Porsolt test, two-bottle test. After the experiments, the animals were killed by decapitation, the brain was extracted, placed in the cold and brain structures (hypothalamus, amygdala) were isolated, immediately frozen in liquid nitrogen and stored at a temperature of -80 C until PCR analysis was performed. RESULTS. Testing of experimental animals in the "Raised cruciform maze" showed that in a group of animals subjected to deprivation from the mother, there was a decrease in the time spent in the open arms of the maze, and the time spent in the closed sleeves increased relative to the control, which can be assessed as an increase in the level of anxiety of animals. In the Porsolt test, the maternal deprivation group had an increased immobilization time relative to the control group of animals. In the maternal deprivation group, under the conditions of a two-bottle sucrose preference test, there was a decrease in sucrose solution preference, which indicates the development of anhedonia. In the hypothalamus, there was a statistically significant decrease in the expression of OX1R mRNA in the experimental group of animals, in contrast to the intact control group. A two-fold decrease in the level of OX1R mRNA expression in the experimental group relative to the control animals was also observed in the amygdala. CONCLUSION. Early stress of maternal deprivation causes a decrease in the expression of OX1R orexin in the hypothalamus and amygdala of the brain and contributes to the development of anxiety-depressive symptoms in rats.