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

Abstract

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.

Effects of BDNF Signaling on Anxiety-Related Behavior and Spatial Memory of Adolescent Rats in Different Length of Maternal Separation

“…The results of the present study found a significant increase in anxiety-like behaviors in rats exposed to PMS but not in offspring exposed to EH. This finding was consistent with a recent meta-analysis showing increased anxiety in rats exposed to PMS, that was more pronounced in younger animals (37). Further, these outcomes supported the notion that more severe forms of stress early in life increased the risk of several behavioral abnormalities, including anxiety, later in life.…”

Voluntary wheel running improves outcomes in an early life stress-induced model of urologic chronic pelvic pain syndrome in male mice

“…Although we did not observe a significant effect of NMS on sucrose preference, the amount of sucrose consumed was increased in naïve-Ex mice and not in NMS-Ex mice, suggesting that exercise had a diminished impact on NMS mice. A recent systematic review and meta-analysis on anxiety-like behaviors in rodent models of NMS revealed increased defensive behavior in rats, but not in mice (74). One of the analyzed tasks included elevated plus maze, which measures exploratory-defense behaviors (42).…”

Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

“…The particular purposes of these meta-analyses are to measure the effect sizes of MS on exploratory-defensive behaviors using an open field test and an elevated plus maze test (the most commonly used tests to evaluate anxiety-like behaviors in rodents), as well as to determine their significance when compared to non-separated controls. Wang et al reported three important points [ 75 ]. First, MS induces a significant increase in exploratory-defensive behaviors in rats, but not in mice.…”