Functional changes and expression of inducible NO synthase in dentate gyrus of rats during modeling of depression and the possibility of their pharmacological correction

Abstract

AbstractBackgroundDepression is seen as the most common cause of disability, and is associated with chronic stress and neuroinflammation. The signaling pathway for the synthesis of nitric oxide plays a crucial role in the neurobiology of mild stress and depression.Methods3 groups were formed: group 1 — control rats (n = 10), group 2 — rats with experimental depression (n = 10), group 3 — rats with experimental depression (n = 10) receiving a compound with the laboratory cipher RSPU‐189 (salifen). The depressive state in animals was caused by exposure to stressful stimuli such as vibration, loud sound and pulsating bright light for 7 days (daily for 30 minutes). The experiment used rats at the age of 12 months. We evaluated the neuropsychiatric state of animals and expression of iNOS in the dentate gyrus.ResultsIn animals of the 2 group, symptoms of depressive behavior were observed, having a pronounced phenomenological similarity to the clinical picture of depression: anxiety, behavioral correlates of despair, inactivity, anhedonia, as well as a decrease in tentative research activity. The use of salifen in rats of group 3 leveled these changes. When evaluating the results of immunohistochemical studies in rats with experimental depression, in contrast to animals of the control group, an increase in the expression level of iNOS‐IRM in granule cells and neuropil in inner polymorphic layer of dentate gyrus was noted. Pharmacological correction of experimental depression by salifen showed a decrease in the expression of iNOS‐IRM to values close to the expression level in the control group of animals.ConclusionsWhen modeling a depressive state in rats of adulthood, an increase in iNOS expression in dentate gyrus is observed, the use of salifen leads to the correction of revealed changes, which may be associated with GABAergic modulation of neurotransmission in the hippocampus. The reported study was funded by RFBR and Administration of Volgograd region according to the research project № 19‐415‐340004∖19.