Effects Of Chronic Unpredictable Stress On The Expression Of DRD2in Prefrontal Cortex Of Rats And Its Possible Mechanism

OBJECTIVETo observe the effects of chronic stress on the body weight, the change of behaviors,expressions of DRD2in prefrontal cortex of rats with chronic unpredictable mildstress-induced depression. And to discuss how chronic stress induce depression and itspossible mechanisms.METHODSTwenty SD rats were devided into two groups: normal group, CUMS group. Rats wereexposed to alternative stress for28days to induce depression.To record the weight ofeach rat in the experimental section first,28th day and compare the weight gain of rat in normal group. The changes of behaviors in rat were observed by determing Sucrosepreference test and immobility time in tail suspension. Using the radio immunoassay(RIA) to detect serum and prefrontal cortex level of cAMP, HE staining was used toobserve changes of the number of neurons in prefrontal cortex of rats. The expression ofDRD2、 PKA、 CREB/p-CREB、 Gαs/Gαi in prefrontal cortex was analyzed byimmunohistochemistry determination.RESULTS1．Effect of chronic stress on body weight and behaviors change of rats with CUMSdepression model.(1) On the1st day, the body weight has no difference in statistical between two groups.On the21st day, compared with normal group, the weight gain decreased markedly inmodel group.(2) On the1st day, the immobility time has no difference in statistical between twogroups. On the21st day, compared with normal group, the immobility time increasedmarkedly in model group.(3) On the1st day, the Sucrose preference test has no difference in statistical betweentwo groups. On the21st day, compared with normal group, the Sucrose preference testdecreased markedly in model group.2. Effect of chronic stress on the expression DRD2of rats with CUMS depressionmodel.DRD2positive cells were observed in each section of prefrontal cortex, the most ofDRD2located Ⅲ~Ⅴ layers of prefrontal cortex, and the DRD2positive reaction existsin cytoplasm and dendrites, not dyed nucleus. The gray value of positive cells decreasedwhile average optical density incresed in model group compared with normal group; theanalysis of western blot revealed the expression of DRD2increased markedly in model group compared with model group.3. Effect of chronic stress on serum and prefrontal cortex level of cAMP in ratswith CUMS depression model.Compared with normal group, the level of serum cAMP decreased markedly in modelgroup; and the level of and prefrontal cortex cAMP also decreased markedly in modelgroup.4. Effect of chronic stress on the expression PKA、CREB/P-CREB of rats withCUMS depression model.PKA and CREB/p-CREB positive cells were observed in each section of prefrontalcortex, the most of positive cells located Ⅲ~Ⅴ layers of prefrontal cortex. The PKApositive reaction exists in cytoplasm, dendrites and cell nucleus; CREB positivereaction exists in dendrites and cell nucleus. The gray value of PKA、CREB positivecells increased while average optical density decresed in model group compared withnormal group; the analysis of western blot revealed the expression of PKA、CREB andP-CREB decreased markedly in model group compared with model group.5. Effect of chronic stress on the expression of Gαs/Gαi rats with CUMS depressionmodel.The analysis of western blot revealed the expression of Gαs increased markedly inmodel group compared with model group, while the expression of Gαi decreasedsignificantly in model group.CONCLUSIONS1. Chronic stress could induced behaviors of rats with the chronic stress depressionmodel inculding reducing sucrose consumption, body weight gain and increasing duration of immobility2. Chronic stress could regulated the expression of DRD2, thereby further change theGαs/Gαi activity and cAMP level, and downregulated the expression of PKA, CREB,p-CREB. The results suggesting chronic stress may be mediated by adjusting DRD2receptor expression and its downstream signaling pathways induced depression behavior,provides the certain laboratory basis for the clinical practice.