Abstract： Objective To investigate the effect of escitalopram on different brain derived neurotrophic factor (BDNF)transcripts and DNA methylation in adult chronic unpredictable mild stress (CUMS) rat hippocampus.Methods The depression model was established with 3-week CUMS.Fifty-six Sprague-Dawley rats were divided into CUMS + water,CUMS + escitalopram,control + water and control +escitalopram group.The depressive-like behaviors were evaluated using a sucrose preference test.Then,the hippocampus BDNF transcripts and DNA methylation of BDNF promoter Ⅳ were detected.Results (1) Sucrose preference test showed that,the sucrose preference was significantly lower in CUMS + water group [ (34±21)％,(63±21)％ ] (post hoc test,P＜0.05) but not in CUMS + escitlopram group[ (58±19)％,(80±14)％ ] (post hoc test,P＞0.05) in comparison with control + water group [ (67±15)％,(80±15)％ ].(2) As to hippocampal BDNF transcripts expression,the expression of exon Ⅳ was the main part of the total BDNF mRNA.Compared with the control + water group [ (6.14±0.87) × 10-3,(6.82±0.35) × 10-3 ],exon Ⅳ and Ⅸ transcripts expression was significantly decreased in the CUMS + water group[ (4.64±0.65) × 10-3,(5.73 ±0.79) × 10-3] (post hoc test,P＜0.05) but not in CUMS +escitlopram group[ (5.69±0.18) × 10-3,(6.91±0.98) × 10-3] (post hoc test,P＜0.05).(3) As to DNA methylation levels,none of the four groups were found methyled in the fourth promoter of BDNF.No significant difference of DNA methylation was found between groups.Conclusions Escitlopram could block the decrease of total hippocampal BDNF transcripts in CUMS adult rats,which mainly due to the increase of the exon Ⅳ transcripts,and the DNA methylation mechanism might not be involved in this process.