| Objective:To explore the effects of YL-IPA08,a highly selective ligand compound of 18 k Da translocator protein(TSPO),on postpartum anxiety-depressive behavior and its potential mechanism.Method:The model of postpartum depression in rats was established by classical hormone simulating post-pregnancy(HSP)hormone withdrawal induced,We divided rats into five groups by their sucrose preference baseline and the effect of YL-IPA08 on spontaneous activity in rats was evaluated by the open field test(OFT),and the effect of YL-IPA08 on anxiety and depressive-like behavior in rats was evaluated by the elevated plus maze test(EPM),Sucrose preference test(SPT)and forced swimming test(FST).The changes of TSPO expression in hippocampus and prefrontal cortex of rats were detected by RT-PCR and Western-blotting.Besides,Enzyme-linked immunosorbent assay(ELISA)was conducted to elucidate the potential molecular mechanism.Result:The levels of TSPO and neurosteroids in the hippocampus and prefrontal cortex of PPD rats were significantly decreased.After 3 weeks of treatment with YL-IPA08,the levels of TSPO and neurosteroids in hippocampus of PPD rats were increased,the anxiety and depressive behaviors of PPD rats were alleviated.Meanwhile,compared with sertraline,a positive control drug,YL-IPA08 has a shorter onset time.?Conclusion:The anxiolytic and anti-depressive activity of YL-IPA08 may be mediated by TSPO through promoting the synthesis of downstream neurosteroids and thus regulating the GABA receptor system and the function of hypothalamus-pituitary-adrenal(HPA)axis.Our results suggest that YL-IPA08 has significant value in the treatment of postpartum depression and TSPO may be a potential new target for the treatment of postpartum anxiety and depression. |
PDF Full Text Request