An overview of maternal separation effects on behavioural outcomes in mice: Evidence from a four-stage methodological systematic review

⿢This systematic review addresses methodological aspects of MS mice studies.⿢There are inconsistencies in findings derived from variations in MS studies.⿢There is many variation regarding timing and duration of MS protocols.⿢Depressive-like behaviour and memory deficits are associated with MS.⿢Balb/c seems to be the more vulnerable strain to MS effects in mice. Early life stress (ELS) developmental effects have been widely studied by preclinical researchers. Despite the growing body of evidence from ELS models, such as the maternal separation paradigm, the reported results have marked inconsistencies. The maternal separation model has several methodological pitfalls that could influence the reliability of its results. Here, we critically review 94 mice studies that addressed the effects of maternal separation on behavioural outcomes. We also discuss methodological issues related to the heterogeneity of separation protocols and the quality of reporting methods. Our findings indicate a lack of consistency in maternal separation effects: major studies of behavioural and biological phenotypes failed to find significant deleterious effects. Furthermore, we identified several specific variations in separation methodological procedures. These methodological variations could contribute to the inconsistency of maternal separation effects by producing different degrees of stress exposure in maternal separation-reared pups. These methodological problems, together with insufficient reporting, might lead to inaccurate and unreliable effect estimates in maternal separation studies.