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Postoperative depression is a serious problem with under-optimized treatment. Our previous result demonstrated that single dose of propofol exposure in mice could cause depressive-like behavior. In the present study, we explored the possible preventive strategy that could ameliorate the depressive-like behavior in mice. Irisin was used for co-treatment with propofol in mice to test whether irisin could prevent the depressive-like behavior in mice. We found irisin could significantly reduce the immobility time in tail suspension and force