Improving oxidative stress response and reversing abnormal expression of hippocampus NET and 5-HTT involved in anti-depressive effect of venlafaxine / 中国药理学通报

ABSTRACT

Aim To investigate if anti-depressive effect of venlafaxine was associated with improving oxi-dative stress and expression of hippocampus NET and 5-HTT in rat model induced by CUS. MethodsEighty SD male rats were randomly divided into four groupsmodel group(MG),normal group(NG), ven-lafaxine-treated normal group ( VNG ) , and venlafax-ine-treated model group ( VMG) . VNG and VMG were given venlafaxine (23. 4 mg·kg-1 ·d-1 ) once daily;NG and MG were given the same volume solvent. Soli-tary condition with chronic unpredicted stress ( CUS ) was taken to establish rat depression model. The force swimming test was used to evaluate the behavior chan-ges of experimental rats. The malondialdehyde ( MDA) level and activity of superoxide dismutase ( SOD ) in serum were determined by biochemical methods. The mRNA and protein expressions of NET and 5-HTT in hippocampus were determined by Real-Time Reverse transcription polymerase chain reaction ( real-time RT-PCR) and Western blot ( WB) , respectively. Results Compared with NG rats, obviously increasing immo-bile time of rats in force swimming test and serum MDA level, as well as significantly decreasing SOD activity in serum was observed with clearly decreasing 5-HTT expression and elevating NET expression in hippocam-pus of MG rats. The treatment of venlafaxine distinctly suppressed changes above from CUS-induced rats. However, significant changes failed to be found in VNG rats. Conclusion The anti-depressive effect of venlafaxine may at least partly involve in improving ox-idative stress/anti-oxidative stress balance and revers-ing abnormal expression of NET and 5-HTT.