Effects of antidepressant therapy on serotonin and tryptophan hydroxylase 2 in ovariectomized rats with depressive disorder

Abstract

Obiective To investigate the effects of antidepressant therapy on whole regulating function of serotonin and tryptophan hydroxylase 2 system in ovariectomized(OVX) rats with depressive disorder. Methods seventy-two female Sprague-Dawley rats were used as subjects.The rats were randomly divided into 8 groups as following: Sham operation group (Sn), depression group(Dn), the OVX group(On), OVX with depression group(ODn), OVX with depression+ sertraline group(ODs), OVX with depression+ citalopram group(ODx), OVX with depression+ venlafaxine group(ODw) , OVX with depression+ reboxetine group(ODr). Rats in group OVX and group OVX with depression were ovariectomized.Rats in group with depression were exposed to the chronic unpredictable mild stress (CUMS). Open-field test and sugar consumption experiment were tested on all rats before the experiment and the 28th day of experiment.The expression of TPH2 mRNA was measured with RT-PCR, and the expression of TPH2 protein was detected by Western blot.The concentration of 5-HT was detected by ELISA. Results (1) After exposure of CUMS, the scores of motion and percentage of sugar consumption experiment in Dn group were decreased contrast to the Sn group(P<0.05) , and the scores in ODn group were decreased compared with the on group(P<0.05). (2)The protein and gene expression of THP2 in On and Dn group were decreased contrast to the Sn group (P<0.05). The protein and gene expression of THP2 in ODn were decreased compared with the on group (P<0.05). The protein and gene expression of THP2 in ODs(protein (0.68±0.07); gene (0.87±0.09)), ODx(protein (0.71±0.05); gene (0.84±0.17)), ODw(protein (0.69±0.04); gene (0.88±0.16)) and ODr(protein (0.53±0.07); gene (0.70±0.15)) were increased compared with the ODn(protein (0.31±0.09); gene (0.56±0.16)) group(P<0.05). (3)The concentration of 5-HT of hippocampus and serum in Dn and On group were decreased contrast to the Sn group (P<0.05). The concentration of 5-HT of hippocampus and serum in ODs, ODx, ODw and ODr group was increased compared with the ODn group (P<0.05). Conclusion The antidepressants can up-regulate the expression of THP2 and the concentration of 5-HT in the OVX rats with depressive disorder.Sertralin is stronger however Reboxetine Mesylate is the poorest. Key words: Antidepressant; Depressive disorder rats model; Ovariectomized rats model; Tryptophan hydroxylase 2; 5-hydroxytryptamine