GOAL

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 was 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, Slc6a3, Pdyn, and Per2), in the prefrontal cortex, hippocampus, and substantia nigra of rats with chronic blockade of D2 receptors by haloperidol, using it as a potential pharmacological model of depression.

MATERIALS AND METHODS

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.

RESULTS

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 the shortened forced swimming test (without haloperidol administration) affects the expression of the genes of interest 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.

CONCLUSION

Thus, in the course of this work, it was shown that chronic blockade of D2 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.