The Role of DRD2-Dependent Genes in the Formation of Depressive Behavior

Clinical depression is of great medical and social importance. At the moment, it is believed that chronic stress is a significant risk factor in the occurrence of depression. In a series of studies, it has been found that the dopamine (DA)ergic system of the brain and its pathways can take part in the reaction to chronic stress, and, accordingly, in the processes of formation and course of depressive episodes. In this regard, the goal of this work was to study the change in expression of both the DA receptor gene Drd2 and Drd2 -dependent genes ( Bdnf , Ntrk2 , S lc6a3 , Pdyn , and Per2 ) in the prefrontal cortex, hippocampus, and substantia nigra of rats with chronic blockade of D 2 receptors by haloperidol, using it as a potential pharmacological model of depression. The study was conducted on 45 male Wistar rats with a potential haloperidol-induced model of depression. The relative level of expression of Drd2 -dependent genes was analyzed by real-time PCR based on TaqMan technology. As a result of the work, it was shown that chronic administration of haloperidol inhibits the expression of the Bdnf , Slc6a3 , and Per2 genes in the prefrontal cortex and Pdyn in the hippocampus, leading to a decrease in the activity of stress adaptation mechanisms in the DAergic system of the brain and the development of a depressive-like phenotype. In addition, we also showed that even slight chronic stress in a shortened forced swimming test (without haloperidol administration) affects the expression of the genes of interest that we have chosen. All genes studied, one way or another, took part in the depression-related stress response; however, Bdnf and Ntrk2 apparently played the most important role. Thus, in the course of this work, it was shown that chronic blockade of D 2 receptors by haloperidol leads to the formation of a depressive-like phenotype in rats and affects the expression of genes involved in the development of depression.