Depression is a complex and biologically heterogeneous disorder. Recent studies have shown that central nervous system (CNS) inflammation plays a key role in the development of depression. Lipopolysaccharide (LPS)-induced depression-like model in mice is commonly used to studying the mechanisms of inflammation-associated depression and the therapeutic effects of drugs. Numerous LPS-induced depression-like models in mice exist and differ widely in animal characteristics and methodological parameters. Here, we systematically reviewed studies on PubMed from January 2017 to July 2022 and performed cardinal of 170 studies and meta-analyses of 61 studies to support finding suitable animal models for future experimental studies on inflammation-associated depression. Mouse strains, LPS administration, and behavioral outcomes of these models have been assessed. In the meta-analysis, forced swimming test (FST) was used to evaluate the effect size of different mouse strains and LPS doses. The results revealed large effect sizes in ICR and Swiss mice, but less heterogeneity in C57BL/6 mice. For LPS intraperitoneal dose, the difference did not affect behavioral outcomes in C57BL/6 mice. However, in ICR mice, the most significant effect on behavioral outcomes was observed after the injection of 0.5 mg/kg LPS. Our results suggests that mice strains and LPS administration play a key role in the evaluation of behavioral outcomes in such models.

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