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.

儿童虐待增加焦虑的机制尚不清楚，但早期生活压力 (ELS) 啮齿动物模型中防御行为增加的倾向表明，在啮齿动物中的工作可能会阐明有关这种关联的重要机制细节。研究 ELS 对啮齿动物防御行为的影响的一个关键挑战是大量不一致的结果。这在母体分离 (MS) 文献中尤为突出，这是啮齿动物中最常用的 ELS 模型之一。为了解决这个问题，我们进行了系统回顾和荟萃分析，使用旷场测试 (OFT) 和高架十字迷宫 (EPM) 检查 MS 对小鼠和大鼠探索性防御行为的影响。这项搜索共产生了 49 项研究，其中 24 项评估了 MS 对 EPM 行为的影响，在 OFT 中测试了 11 项行为，14 项研究提供了这两项任务的数据。MS 与大鼠的防御行为增加有关（EPM：Hedge'sg  = -0.48，p  = 0.02；OFT：Hedge 的g  = -0.33，p  = 0.05），效应大小与人类报告的早期逆境的焦虑效应一致。相比之下，MS 并未改变小鼠的探索行为（EPM：Hedge 的g  = -0.04，p  = 0.75；OFT：Hedge 的g  = -0.03，p  = 0.8）。研究之间存在相当大的异质性，这可能与 MS 协议缺乏标准化有关。总之，这些发现表明 MS 改变调节小鼠和大鼠防御行为的电路的能力存在重要差异。