OBJECTIVE To detect whether YL-IPA08, a new TSPO ligand designed and synthesized by our institute, may be effective in the treatment of PTSD.METHODS We first assessed the effects of YL-IPA08 in alleviating the enhanced anxiety and fear response induced in the inescapable electric foot shock-induced mouse model of PTSD and the time-dependent sensitization (TDS) procedure, a rat PTSD animal model.In an effort to explore the role of TSPO in mediating the antiPTSD effect of YL-IPA08, we then tested whether blocking the TSPO ligand with a TSPO antagonist, PK11195;either alone or in combination with YL-IPA08 treatment,affected the behavioral effect of YL-IPA08 in post-TDS rats.Furthermore, the changes of Allo in the serum and prefrontal cortex after chronic YL-IPA08 administration were also assessed in TDS-treated rats.RESULTS In the present study, we showed that chronic treatment with YL-IPA08 caused significant suppression of the enhanced anxiety and contextual fear induced in the inescapable electric foot-shock induced mouse model of PTSD and the TDS procedure in rats; these effects were completely blocked by the TSPO antagonist PK11195.Furthermore,YL-IPA08 treatment increased the levels of Allo in the prefrontal cortex and serum of post-TDS rats and these effects were antagonized by PK11195.CONCLUSION In summary, the findings from the current study showed that YL-IPA08, a potent and selective TSPO ligand, had a clear anti-PTSD-like effect, which might be partially mediated by binding to TSPO and the subsequent synthesis of allopregnanolone.