OBJECTIVE To investigate the effects of silent information regulator 1 (SIRT1) in amygdala on depression-like behaviors in rats using chronic restraint stress (CRS) as a model of depression. METHODS Sixty male SD rats were randomly divided into six groups (n=10 per group): control group (Control), chronic restraint stress group (CRS), CRS + fluoxetine-treated group (CRS + FLU), CRS + saline-treated group (CRS + NaCl), CRS + SIRT1-overexpression group (CRS + AAV-SIRT1), and CRS + empty vector group (CRS + AAV-EGFP). Except for the control group, rats from the other groups were exposed to chronic restraint stress for 21 days. After the modeling, rats in fluoxetine-treated group and saline-treated group were, respectively, treated with fluoxetine (10 mg/kg) or saline (10 mg/kg) by gavage every day for 3 weeks; AAV-SIRT1 or AAV-EGFP was, respectively, stereotaxically injected into the amygdala of rats in SIRT1-overexpression group and empty vector group, and the virus was expressed for 3 weeks. Rats in normal control group and CRS model group were not given any drug treatment. The depression-like behaviors of rats in each group were evaluated by sugar preference test (SPT), open field test (OFT) and forced swimming test (FST). SIRT1 expression in amygdala of rats was assessed by using immunoblot blotting. The number of SIRT1-positive cells in amygdala of rats was detected by immunofluorescence technique. RESULTS Compared with the normal control group, the level of SIRT1 protein and the number of SIRT1+ cells in amygdala of the CRS-exposed rats were decreased significantly (P＜0.01), and CRS-exposed rats showed a significant decrease in sucrose preference (P＜0.01), less total horizontal distance (P＜0.01) and less time entered the center field (P＜0.01) in the OFT, a significant increase in the immobility time of the FST (P＜0.01). Fluoxetine treatment (P＜0.05, P＜0.01) or SIRT1 overexpression (P＜0.01) partially reversed the down-regulation of SIRT1 protein and SIRT1+ cells in amygdala of CRS-exposed rats and significantly improved the depression-like behaviors of CRS rats. CONCLUSIONS Fluoxetine treatment partially reversed the down-regulation of SIRT1 level and the number of SIRT1+ in CRS rats, and significantly improved the depression-like behaviors. The antidepressant effect of fluoxetine treatment may be related to the up-regulation of SIRT1 in the amygdala of CRS-exposed rats.