Effect of Translocator Protein Ligand YL-IPA08 on Anxiety-Depressive-Like Behavior in Postpartum Depression Rats / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the effect of Mr1.8×104 translocator protein (TSPO) selective ligand compound YL-IPA08 on postpartum anxiety-depressive behavior. METHODS: The model of postpartum depression in rats was established by classical hormone simulating postpregnancy (HSP) hormone withdrawal induced, 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) and forced swimming test (FST). The changes of TSPO expression in hippocampuls and prefrontal cortex of rats were detected by RT-PCR and Western blot. RESULTS: Compared with control group, the hormones of pregnancy hormones withdraw stimulating and drug treatment do not affect the spontaneous activity of rats (P>0.05), but the model group rats showed significant anxiety and depressive symptoms, which is characterized by elevated plus maze test (P<0.05, P<0.01),and forced swimming test (P<0.05).After the establishment of the model, three weeks of intragastric administration were started, YL-IPA08 (0.1 and 0.3 mg•kg-1, po) or positive control drug sertraline (10 mg•kg-1, po) can significantly reverse the above series of changes of postpartum anxiety and depressive behavior (P<0.05 or 0.01), and significantly increase the TSPO level in the hippocampus and prefrontal cortex of the model rats. CONCLUSION: YL-IPA08 shows anti-postpartum anxiety-depressive behavior in a series of rat behavior models, and the mechanism may be closely related to its enhancing central TSPO expression and promoting biosynthesis of following neurosteroids.