Improvement of oxidative stress and HPA axis function and elevation of BDNF expression involved in anti-depressive effect of paroxetine in rat model

Abstract

Abstract: AIM: To investigate the correlation between antidepressive effect of paroxetine and improvements of oxidative stress, brain-derived neurotrophic factor (BDNF) expression and the hypothalamic-pituitary- adrenal (HPA) axis function in rat model induced by chronically unpredicted mild stress (CUMS). METHODS: 60 male SD rats were randomly divided into following groups: normal group (NG), model group (MG), normal group-treated with 1.8 mg·kg^-1·d^-1 paroxetine (PNG), and model group-treated with paroxetine (PMG). Chronic mild unpredicted stress (CUMS) with solitary condition was taken to establish rat depression model. The open-field test and sucrose consumption were used to evaluate the behaviour changes of experimental rats. The malondialdehyde (MDA) levels, activities of superoxide dismutase (SOD) and catalase (CAT), corticosterone (CORT) in serum, and expressions of BDNF in hippocampus and CRF in hypothalamus were determined by reagent kits, radio-immunoassay, and reverse transcription polymerase chain reaction (RT-PCR),respectively.RESULTS: There were significant decreases of locomotor activities and sucrose water consumption, significantly increasing serum MDA and CORT levels with clearly decreasing SOD and CAT activities,and obviously decreasing expressions of BDNF and elevated CRF expression in model group, compared with NG. The treatment of paroxetine obviously improved the changes above induced by CUMS. However treatment of paroxetine had no significant influences on either behaviors or indices of NG rats.CONCLUSION: The antidepressive effect of paroxetine may involve in the improvements of oxidative stress/antoxidative stress balance, HPA axis function, and the expression of BDNF.

Key words: CUMS, Depression model, Paroxetine, BDNF, HPA axis

CLC Number:

R965.2

FEI Hui-zhi, WANG Han, HU Xiao-ya, LI Na, WEN Wei, YAN Tao, ZHOU Qi-xin. Improvement of oxidative stress and HPA axis function and elevation of BDNF expression involved in anti-depressive effect of paroxetine in rat model[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(10): 1137-1142.

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