BackgroundAcute myocardial infarction (AMI) is a main cause of death all around the world. There is a close relationship between myocardial infarction (MI) and depression. MI patients with untreated depression had higher mortality than those without depression. Therefore, this study aimed to explore the effect of escitalopram in treating a model under MI and unpredictable chronic mild stress (UCMS).MethodsMale C57BL/6J mice were treated with sham surgery, or MI surgery, or UCMS, or escitalopram (ES) for a consecutive two weeks. And the mice were divided into Sham group, MI group, MI + UCMS group, MI + UCMS + ES group (n= 8 in each group). After treatment, the mice went through open field test for anxiety behavior, sucrose preference test for depressive behavior. After sacrificed, the blood, heart, hippocampus, and cortex were collected.ResultsThe escitalopram badly increased the area of cardiac fibrosis size. The sucrose preference test demonstrated that escitalopram treatment showed significant effect in improving depressive behaviors of mice under MI + UCMS. The potential mechanism involved the interrelation between 5-HT system and inflammation. MI significantly affected the level of cardiac SERT. Both UCMS and ES significantly affected the level of cortex TNF-α. UCMS significantly affected the level of cardiac IL-33. In the hippocampus tissue, TNF-α was positively correlated with SERT, and IL-10 was positively correlated with SERT. In the cortex tissue, IL-33 was positively correlated with 5-HT4R, and sST2 was positively correlated with 5-HT.ConclusionsTwo-week escitalopram treatment might worsen myocardial infarction. But escitalopram could benefit depressive behaviors, which may be related with the interrelationship between the 5-HT system and inflammatory factors in the brain.