Curculigoside (CUR) is the main active component of traditional Chinese medicine Curculigoorchioides Gaertn (Xianmao in Chinese),which exhibits a variety of pharmacological activities.In this study we investigated the effects of CUR on fear extinction and related depression-like behaviors in mice.In fear conditioning task,we found that administration of CUR (1.6,8,40 mg·kg-1·d-1,ip,for 7 days) did not affect memory consolidation,but CUR at higher doses (8,40 mg·kg-1·d-1) significantly facilitated fear extinction,especially on D3 and D4.Moreover,CUR administration significantly ameliorated the fear conditioning-induced depression-like behaviors,likely through promoting fear extinction.We showed that CUR increased the expression of brain-derived neurotrophic factor (BDNF) and phosphorylation of tropomyosin receptor kinase B (TrkB) in the hippocampus,and activated protein kinase B (Akt)-mammalian target of the rapamycin (mTOR) signaling pathway.Administration of the selective TrkB agonist 7,8-dihydroxyflavone (7,8-DHF,5 mg·kg-1·d-1,ip) also facilitated fear extinction,ameliorated depression-like behaviors.We established a mouse leaed helplessness (LH) model to evaluate the antidepressant activity of CUR.The spatial memory was assessed in Morris water maze.We showed that LH-induced depression-like behaviors,including prolonged immobility times in forced swim and tail suspension tests as well as spatial memory impairments;LH also downregulated BDNF expression and the Akt-mTOR signaling pathway in the hippocampus.Administration of CUR (1.6,8,40 mg·kg-1·d-1,ip,for 14 days) or 7,8-DHF (5 mg·kg-1·d-1,ip,for 3 days) prevented LH-induced depression-like behaviors and promoted BDNF expression and the Akt-mTOR signaling pathway.In conclusion,CUR can accelerate the fear memory extinction and ameliorate depression-like behaviors in mice via promoting BDNF expression and activating the Akt-mTOR signaling pathway in the hippocampus.