Objective To evaluate the effect of propofol on autophagy in hippocampal neurons of mentally depressed rats after electroconvulsive (ECT) therapy.Methods Healthy adult male Sprague-Dawley rats,aged 2-3 months,weighing 200-250 g,were used in this study.Mental depression was induced by exposing the rats to chronic unpredictable mild stress (CUMS).Forty mentally depressed rats were randomly divided into 4 groups (n =10 each):depression group (group D),propofol group (group P),ECT group (group E),and propofol + ECT group (group PE).Groups D and P received intraperitoneal normal saline 8 ml/kg and propofol 80 mg/kg,respectively,once a day for 7 consecutive days.Group E received intraperitoneal normal saline 8 ml/kg once a day for 7 consecutive days and then received ECT once a day for 7 consecutive days.Group PE received intraperitoneal propofol 80 mg/kg and then received ECT once a day for 7 consecutive days after the righting reflex disappeared.Before CUMS,after CUMS (before ECT) and after the end of ECT (T1-3),sucrose preference test was performed to assess depression,and Morris water maze was performed to assess the learning and memory abilities.The rats were sacrificed after completion of Morris water maze and hippocampi were removed for determination of the expression of Beclin-1 and LC3-Ⅱ in CA1 region.Results Compared with the baseline value at T1,the sucrose preference percentage was significantly decreased at T2 in all the groups.Compared with group D,the sucrose preference percentage was significantly increased,the escape latency was prolonged,space exploration time was shortened,and the expression of Beclin-1 and LC3-Ⅱ in hippocampal CA1 was up-regulated at T3 in E and PE groups.Compared with group E,the escape latency was significantly shortened,space exploration time was prolonged,and the expression of Beclin-1 and LC3-Ⅱ in hippocampal CA1 was down-regulated at T3 in group PE.Conclusion The mechanism by which propofol ameliorates cognitive impairment induced by ECT may be related to inhibition of activation of autophagy in hippocampal neurons of mentally depressed rats. Key words: Propofol; Depression; Electroconvulsive therapy ; Neurons; Autophagy