Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents

The mechanisms by which childhood maltreatment increases anxiety is unclear, but a propensity for increased defensive behavior in rodent models of early life stress (ELS) suggests that work in rodents may clarify important mechanistic details about this association. A key challenge in studying the effects of ELS on defensive behavior in rodents is the plethora of inconsistent results. This is particularly prominent with the maternal separation (MS) literature, one of the most commonly used ELS models in rodents. To address this issue we conducted a systematic review and meta-analysis, examining the effects of MS on exploratory-defensive behavior in mice and rats using the open field test (OFT) and the elevated plus maze (EPM). This search yielded a total of 49 studies, 24 assessing the effect of MS on behavior in the EPM, 11 tested behavior in the OFT, and 14 studies provided data on both tasks. MS was associated with increased defensive behavior in rats (EPM: Hedge's g = -0.48, p = 0.02; OFT: Hedge's g = -0.33, p = 0.05), effect sizes that are consistent with the anxiogenic effect of early adversity reported in humans. In contrast, MS did not alter exploratory behavior in mice (EPM: Hedge's g = -0.04, p = 0.75; OFT: Hedge's g = -0.03, p = 0.8). There was a considerable amount of heterogeneity between studies likely related to the lack of standardization of the MS protocol. Together, these findings suggest important differences in the ability of MS to alter circuits that regulate defensive behaviors in mice and rats.