Establishment Of Learning And Memory Impairement Rat Model And Depression Rat Model And The Antidepressant-Like Effect Of DS-1226

ObjectiveTo establish rats model of learning and memory Impairement and depression rat model caused by chroninc restraint, and investigate the antidepressant-like effect and mechanism of DS-1226on chronic restraint ratsMethods1. Establishment of learning and memory impairement rats model caused by chroninc restraint:The rats (male, female) were restraint for14hours per day for14days and28days respectively. Behavioral and pharmacological experiment was used to evaluate learning and memory ability of restraint rats.2. Establishment of depression rats model caused by chroninc restraint: The rats (male, female) were restraint10/14hours per day for28days. Using behavioral and pharmacological expriment to observe whether chroninc restraint rats were depressive.3. The antidepressant-like effect and mechanism of DS-1226on chronic restraint rats:Pre-treat the chronic rats with DS-1226and using behavioral and pharmacological experiment to evaluate the antidepression-like effect of various dose DS-1226, then use ELISA to measure serum cortisone levels and5-HT levels in cerebral cortex, and Westernblot to detect11-HSD1, GR,CREB, BDNF expression levels in cerebral cortex to reascher the mechanism of antidepressant-like effect of DS-1226.Results1. Establishment of learning and memory Impairement rats model caused by chroninc restraint:There is no difference between control group and model group without the reduce of weight and spontaneous activity in centre area of male model rats in14h/14d CRS.However, both male and female rats in14h/28dCRS show the total distance and total time in Morris water maze test is obviously longer than control group.2. Establishment of depression rats model caused by chronicrestraint: the sucrose consumption index (%), explore behavior to novel object, spontaneous activity in centre area, nose poke to reward food(n), and body weight of male and female model rats of14h/28dCRS were significantly reduced than control groups, which are performance of depression.3. The antidepressant-like effect and mechanism of DS-1226on chronic restraint rats:DS-1226can increase sucrose consumption index(%), explore behavior to novel object, nose pokes to reward food(n), spontaneous activity in centre area and body weight, and reduce latent time(s)to novel object of chronic restraint rats.(2) Serum cortisone levels and11(3-HSD1expression in cerebral cortex was significant increased, and CREB,BDNF expression in cerebral cortex was reduced in model rats. DS-1226can reversal such changes caused by chronic restraint. However,5-HT and GR expression levels in cerebra cortex have no remarkbalely different in each groups.Conclusions1. The rats (male and female) were restraint forl4hours per day for28days consecutively can lead to learning and memory dysfunction and depression.2. DS-1226has showed antidepressant-like effect on chronic restraint rats. It maybe through reduce cerebral cortex cortisone levels by inhibit11β-HSD1expression in brain and decrease serum cortisone levels, protect and promote nerve cell growth by increase CREB, BDNF expression levels in brain to achieve the antidepressant-like effects.