Relationship Between The Antidepression Effect Of Venfalaxine And The Expression Of BDNF,NET,5-HTT And The Function Of HPA Aix

Objective:The aim of this thesis was to investigate if anti-depressive effect ofvenlafaxine was associated with the expression of BDNF,NET,5-HTT andthe hypothalamic-pituitary-adrenal(HPA) axis function in rat modelinduced by CUMS.Method:1. Four following groups were established by divided80SD male ratsrandomly: normal group(NG),model group(MG),normal group treated withvenlafaxine(VNG),and model group treated with venlafaxine(VMG).2.solitary condition with Chronic mild unpredicted stress(CUMS) wastaken to establish rat depression model.VNG and VMG were givenvenlafaxine23.4mg/kg/d once daily,NG and MG were given the samevolume solvent.3. The open-field test,force swimming test and sucrose consumptiontest were used to evaluate the behaviour changes of experimental rats.4. The changes of hippocampus were observed by pathological sliceswith HE staining under microscope. 5. The malondialdehyde (MDA) levels, activities of superoxidedismutase (SOD) and catalase (CAT) in serum and hippocampus weredetermined by biochemical methods. radio-immunoassay was used todeterminate corticosterone (CORT) level in serum. The expressions ofBDNF in cortex, CRF in hypothalamus, and NET,5-HTT in hippocampus,were determined by Real-Time Reverse transcription polymerase chainreaction (real-time RT-PCR) and Western blot(WB), respectively.Results:1. There was a significant decrease of locomotor activities in open-fieldand a significant increase of rest time form force swimming in model groupin compared with normal control group. There existed a decreasing trend ofsucrose water consumption in MG rats, but no statistical significance wasobserved (MG vs NG). The treatment of venlafaxine obviously improvedthe anxiety-and depression-like symptoms of rats caused by CUMS.2. Compared with NG rats, an clear karyopyknosis and highlyconcentrated chromatin of hippocampal neurocytes were observed inpathological slices of MG. The treatment of venlafaxine seemed to relievethe pathological changes in hippocampus.3. Compared with NG rats, MDA level from both serum andhippocampus, and serum CORT level were increased significantly; SODand CAT activities in both serum and hippocampus were clearly decreasing;expression of hypothalamus CRF and hippocampus NET were obviously elevated. At the same time, the expression of cortex BDNF andhippocampus5-HTT were markedly reduced in MG rats. The treatment ofvenlafaxine distinctly suppressed above changes from CUMS-induced rats.Conclusion:The antidepressive effect of venlafaxine may at least partly involve inthe improvements of oxidative stress/antoxidative stress balance, HPA axisfunction, and the expression of BDNF, NET and5-HTT.