Anti-post-traumatic-stress-disorder effects of YL-IPA08, a selective 18kDa translocator protein ligand / 国际药学研究杂志

ABSTRACT

Objective To explore the anti-post-traumatic-stress-disorder(anti-PTSD)effects of YL-IPA08,a selective 18kDa translocator protein(TSPO)ligand.Methods The time-dependent stress sensitization(TDS)method was used to establish a rat mod?el of PTSD.The open field test(OFT)was used to evaluate the locomotor activity in rats.The contextual freezing(CF)measurement, elevated plus maze(EPM)test and novel objective recognition(NOR)test were used to evaluate the PTSD-like behaviors in rats.The concentration of allopregnanolone in rat hippocampus was detected by ELISA. Results Compared with the control group,neither TDS nor drug treatment affected the locomotor activity in rats(P>0.05).However,PTSD rats showed significant PTSD-like behaviors with enhanced CF time in CF mearsurement,decreased open arm time and open arm entries in EPM test,and dropped object recogni?tion index in NOR test(P<0.05 or 0.01).Moreover,the concentration of hippocampus allopregnanolone was decreased in PTSD rats (P<0.05).YL-IPA08(0.05-0.1mg/kg)or positive drug sertraline(15 mg/kg),administered intragastrically after establishment of PTSD model,significantly reversed the above PTSD-like behavioral changes(P<0.05 or 0.01)and increased the concentration of hip?pocampus allopregnanolone in PTSD rats.Conclusion YL-IPA08 could improve the PTSD-like behavior in rats,and the mechanism may be related to the increased allopregnanolone level in hippocampus.