Neonatal maternal separation affects metabotropic glutamate receptor 5 expression and anxiety‐related behavior of adult rats

Abstract

Exposure to early life stress leads to long-term neurochemical and behavioral alterations. Stress-induced psychiatric disorders, such as depression, have recently been linked to dysregulation of glutamate signaling, mainly via its postsynaptic receptors. The role of metabotropic glutamate receptor 5 (mGluR5) in stress-induced psychopathology has been the target of several studies in humans. In rodents, blockade of mGluR5 produces antidepressantlike actions, whereas mice lacking mGluR5 exhibit altered anxiety-like behaviors and learning. In this study, we used well-known rodent models of early life stress based on mother-infant separation during the first 3 weeks of life in order to examine the effects of neonatal maternal separation on mGluR5 expression and on anxiety-related behavior in adulthood. We observed that brief (15 min) neonatal maternal separation, but not prolonged (3 h), induced increases in mGluR5 mRNA and protein expression levels in medial prefrontal cortex and mGluR5 protein levels in dorsal, but not ventral, hippocampus of adult rat brain. Behavioral testing using the open-field and the elevated-plus maze tasks showed that brief maternal separations resulted in increased exploratory and decreased anxiety-related behavior, whereas prolonged maternal separations resulted in increased anxiety-related behavior in adulthood. The data indicate that the long-lasting effects of neonatal mother-offspring separation on anxiety-like behavior and mGluR5 expression depend on the duration of maternal separation and suggest that the increased mGluR5 receptors in medial prefrontal cortex and hippocampus of adult rats exposed to brief neonatal maternal separations may underlie their heightened ability to cope with stress.

Sex-specific behavioral outcomes of early-life adversity and emerging microglia-dependent mechanisms

“…Some studies using MS as a model for ELA have shown increased anxiety-like behavior in MS mice, particularly in males (Daniels et al, 2004 ; Malcon et al, 2020 ; Tsotsokou et al, 2021 ), although this is inconsistent (Fabricius et al, 2008 ; Bondar et al, 2018 ; Wang D. et al, 2020 ). On the other hand, numerous studies applying the LBN model have found that exposure to ELA does not affect anxiety-like behavior in the open field or elevated-plus maze test in male rats and mice (Naninck et al, 2015 ; Molet et al, 2016a ; Bolton et al, 2018a ; Bolton et al, 2020 , Figure 1B ).…”

At the Crossroad Between Resiliency and Fragility: A Neurodevelopmental Perspective on Early-Life Experiences

“…Given these findings, the protracted consequences of eLA on adulthood emotional regulation are less intuitive. On one hand, increased anxiogenic behaviors and altered fear regulation are consistently detected in adult rodents with history of eLA, irrespectively from the kind of stressors (Brenhouse and Bath, 2019;Guadagno et al, 2020;Manzano Nieves et al, 2020;Tsotsokou et al, 2021). On the other hand, surprising findings are observed in the cortico-limbic pathway.…”

Enriched environment alleviates adolescent visceral pain, anxiety- and depression-like behaviors induced by neonatal maternal separation

“…Neonatal exposure to stressful environments is widely believed to be associated with impairments in brain development and adult behavior. Early life stress significantly increases the risk of visceral hypersensitivity and psychiatric disorders (1)(2)(3)(4). Both physical abuse and mental neglect in childhood are key environmental risk factors associated with the development of visceral pain and multiple psychiatric disorders, such as major depressive disorder and anxiety disorders (5).…”