Relationships Between Antidepressive Effect Of Paroxetine And Expressions Of BDNF,CRF,NET,and 5-HTT In Rats

Objective:To investigate antidepressive effect of paroxetine and its connection with expressions of BDNF , CRF , NET ,and 5-HTT in depression model of rats induced by CUMSMethods :1. CUMS with solitude was taken to establish rat depression model.2. Open-field assay, sugar consumption ,and elevated plus-maze test were used to evaluate the changes of depressive behavior from experimental rats.3.Biochemical methods were taken to determine activities of SOD and CAT, and MDA content in serum and cortex. Radioimmunoassay was used to test CORT level of serum. Immunohistochemistry staining,RT- PCR, and western blot were used to evaluate expressions of BDNF and 5-HTT in hippocampus,NET in pons cerebelli, and CRF in hypothalamus. Pathological slices with HE staining were taken to observe change of hippocampus. Results:1. There were significant decreases of crossing,rearing,and grooming activities in open-field test,sucrose consumption,and activity and retention time in elevated plus maze in model group ( MG) ,compared with NG. The treatment of paroxetine obviously improved the symptoms of rats caused by CUMS. However treatment of paroxetine had no influences on behaviors of NG rats.2. Significantly increasing levels of MDA and CORT ,clearly decreasin g activities of SOD and CAT, and obviously decreasing expressions of NET ,5- HTT, BDNF ,and CRF were determined in MG in comparison of NG. The treatment of paroxetine markedly inhibited the changes above. The treatment of paroxetine did not affect levels of MDA and CORT, activities of SOD and CAT, and NET ,5-H TT, BDNF ,and CRF in NG rats.3. An obvious karyopyknosis of hippocampal neurocytes was observed in model group, compared with NG. The treatment of paroxetine significantly relieved the pathological changes.Conclusion:CUMS can induce depression behaviors, the mechanism of which may involve in the imbalance of oxidative stress and anti-oxidative systems , increasing CORT, decreasing expressions of NET, 5-H TT, and BDNF. The treatment of paroxetine can improve the depressive behaviours of rats caused by CUMS through reversing the imbalance of oxidative stress and anti- oxidative systems, elevating the low expressions of 5- HTT, NET, and BDNF,and blunting high expression of CRF and high serum level of CORT. Paroxetine has no influence on the neuropsychiatry of health rats.