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Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT1R) plays a potential pathophysiological role in several types of CNS disorders.Our previous study has shown that knockdown of hippocampal CysLT1R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS).Here,we examined the effects of hippocampal CysLT1R knockdown and CysLT1R blockade on LPS-induced depressive-like behavior in mice.We found that injection of LPS (0.5 mg/kg,ip) caused marked increase in hippocampal CysLT1R expression,which was reversed by pretreatment with fluoxetine (20 mg·kg1·d-1 for 7 d,ig).Knockdown of hippocampal CysLT1R or blockade of CysLT1R by pretreatment with pranlukast (0.5 mg/kg,ip) significantly suppressed LPS-induced depressive behaviors,as evidenced by decreases in mouse immobility time in the forced swimming test (FST) and tail suspension test (TST) and latency to feed in the novelty-suppressed feeding (NSF) test.Moreover,both CysLT1R knockdown and CysLT1R blockade markedly prevented LPS-induced neuroinflammation,as shown bythe suppressed activation of microglia and NF-κB signaling as well as the hippocampal levels of TNF-α and IL-1β in mice.Our results suggest that CysLT1R may be involved in LPS-induced depressive-like behaviors and neuroinflammation,and that downregulation of CysLT1R could be a novel and potential therapeutic strategy for the treatment of depression,at least partially due to its role in neuroinflammation.