Effect Of Saponins Of Rhizoma Polygonati On The Pathway Of5-HT1AR/cAMP/PKA/CREB In Rats With Chronic Stress Induced Depression And Its Possible Mechanism

OBJECTIVE1. Through observe the behaviors of rats with chronic stress induced depression tofurther defined the anti-depression effect and its possible mechanism of SRP.2. Through observe the expressions of5-HT1AR、cAMP、PKA、CREB in hippocampusand cerebral cortex of rats with chronic unpredictable mild stress-induced depression.To explore the anti-depression effect and its possible mechanism of SRP.METHODSSixty SD rats were randomly divided into six groups: normal control group, depressionmodel group, SRP (100,200,400mg/kg) groups, fluoxetine(2mg/kg) group. And for thegroups of normal and model group, rats were given an equal volume of vehicle (CMC-Na) at the same time,and other groups were given SRP under the definite dose.To record the weight of every rat in the experimental section first,21st day and comparethe weight gain of rat in each group. The changes of behaviors in rat were observed bydeterming autonomous activity, sugar water consumption. cAMP level of hippocampusand cerebral cortex were detected by radioimmunoassay. The expression of5-HT1AR,PKA, CREB in the hippocampus was determined by immunohistochemistry.RESULTS1．Effect of SRP on body weight of rats with chronic stress depression.On the1st day, the body weight of rats was no significance. On the21st day, the weight gainof model rats were markedly less than that of normal group, the weight gain of rats inthree doses of the SRP all increased compared with model control.2. Effect of SRP on behaviors of rats with chronic stress depression.(1) On the1st day, the autonomic activities was no significance. On the21st day, comparedwith normal group, decreased markedly in model and SRP(100,200mg/kg) group;compared with model group, autonomic activities increased in SRP(200,400mg/kg) andfluoxetine(2mg/kg) group.(2) On the1st day, the immobility time in tail suspension was no significance. comparedwith normal group, the immobility time in tail suspension increased markedly in modelgroup; compared with model group, the immobility time in tail suspension decreased inSRP(100,200,400mg/kg) and fluoxetine(2mg/kg) group.(3) On the1st and7st day, the consumption of sugar water was no significance. On the14stand21st day, Compared with normal group, the consumption of sugar water decreasedmarkedly in model and SRP100mg/kg group; compared with model group, theconsumption of sugar water increased in SRP(200,400mg/kg) and fluoxetine(2mg/kg)group. 3.The effects of SRP on the expression of5-HT1AR in hippocampus and cerebralcortex of rats with chronic stress depressionCompared with normal group, average optical density decreased significantly in modeland SRP100mg/kg group; compared with model group, average optical densitysignificantly increased in SRP(200,400mg/kg) and fluoxetine(2mg/kg) group.4.The effects of SRP on the level of cAMP in hippocampus and cerebral cortex ofrats with chronic stress depressionCompared with normal group, the level of cAMP decreased significantly in model andSRP100mg/kg group; compared with model group, the level of cAMP significantlyincreased in SRP(200,400mg/kg) and fluoxetine(2mg/kg) group.5.The effects of SRP on the expression of PKA、CREB in hippocampus and cerebralcortex of rats with chronic stress depressionCompared with normal group, the expression of PKA、CREB decreased significantly inmodel and SRP100mg/kg group; compared with model group, the expression of PKA、CREB significantly increased in SRP(200,400mg/kg) and fluoxetine(2mg/kg) group.5-HT1AR、PKA、CREB positive cells were observed in each section of hippocampus andcerebral cortex, the most of5-HT1AR located Ⅲ~Ⅴ layers of cerebral cortexa, the mostof PKA、CREB located Ⅱ~Ⅵ layers of cerebral cortexa, pyramidal cell and granular celllayer (gcl) of CA1and CA3in hippocampus.CONCLUSIONS1. SRP could improve behaviors of rats with chronic stress depression. It suggested thatSRP may improve depressive symptoms.2. SRP can through the pathway of5-HT1AR/cAMP/PKA/CREB to playanti-depression effect. Suggest that the abnomal of5-HT1AR/cAMP/PKA/CREB singal path may be. SRP can upregulate the singal path may be the major mechanism ofanti-depression effect.