Piromelatine Ameliorates Chronic Mild Stress Induced Depression Behavior In Rats

Object: Long-term chronic stress can cause depression, anxiety and other emotional abnormalities.The hippocampus is an important part of the limbic system that is cognition key brain regions,it play an important role in the mood to mediate to regulate human emotion, memory.Some studies have shown that hippocampal neurogenesis play a key role in depression disease. Piromelatine is a new type of synthetic melatonin receptor agonist that widely distributed in the central nervous system with a variety of physiological activity, it has anti-anxiety, antidepressant effect. It is new drug with broad application.This experiment based on chronic mild stress depression animal models, Determined by sucrose intake test and other behavioral tests measuring plasma corticosterone levels are measured to assess whether Piromelatine antidepressant effece, by immunohistochemistry BrdU marked newborn neurons, BrdU-positive cells in hippocampus DG area count neurogenesis plays in Piromelatine mechanism of antidepressant action.Methods: The CMS model is established by chronic mild stress treated seven weeks in rats, the first five weeks according to the results of sucrose consumption test in rats The rats were divided into non-stressed vehicle group, non-stress piromelatine group, CMSA vehicle group, CMSA piromelatine group, CMSR vehicle group and CMSR piromelatine group. the last two weeks of the Chronic mild stress intraperitoneally piromelatine(50mg / kg) treatment, one time per day. Chronic mild stress last one week intraperitoneally BrdU(50mg / kg) treatment, performed in one hour before the injection Piromelatine, one times per day, and detect the sucrose intake per week in rats; 7th row weekend tail suspension test, forced swimming test and other behavioral tests, After the end of the behavioral tests taken via the tail vein blood, ELISA method with plasma corticosterone detection, and then the rats were sacrificed, weighed and calculated rat adrenal weight ratio; 4% paraformaldehyde isolated brain tissue by heart perfusion, immunohistochemical staining detect newborn neurons with marked BrdU and then BrdU-positive cells were counted.Results:The results show, piromelatine can significantly ameliorates CMS induced stress sensitive groups consume sugar levels lower, tail suspension test and forced swim test immobility time prolonged, adrenal weight ratio increased and the expression of BrdU-positive cells in DG reduction. piromelatine can significantly reduce the stress group and unstressed plasma corticosterone levels; piromelatine resist peer group in addition to stress in plasma corticosterone alia testing parameters were not significantly affected.Conclusion: The above results show that, Piromelatine ameliorates chronic mild stress induced depression behavior in rats, which may be related piromelatine promote hippocampal neurogenesis in DG.