Abstract

Maternal separation (MS) early in life is related to an increase in anxiety and depressive-like behaviors and neurobiological alterations mostly related to alterations in hypothalamic pituitary adrenal (HPA) axis reactivity. Environmental enrichment (EE) has been used to ameliorate the effects of MS. However, the outcomes of this intervention at different developmental periods after MS have not been studied. We subjected male and female Sprague–Dawley pups to MS and subsequently compared the effects of EE started either in the pre-pubertal period [postnatal day (PND) 22] or adulthood (PND 78). Anxiety and depressive-like behaviors as well as in hippocampal synaptic density and basal corticosterone, oxytocin, and vasopressin levels were measured. Our results support the beneficial effects of adulthood EE in decreasing anxiety in males as well as promoting synaptic density in ventral hippocampal CA3. Males displayed higher levels of vasopressin while females displayed higher oxytocin, with no changes in basal corticosterone for any group after EE.

Highlights

  • The maternal separation (MS) model is a well-validated rodent model that mimics early life neglect/loss in humans (Plotsky and Meaney, 1993)

  • Mice subjected to MS from post-natal day (PND) 2 to 15 showed a decrease in time spent in the center in the open field test (OFT) as well as a decrease in the latency to immobility and an increase in total immobility time in the forced swim test (FST), suggesting increased anxiety and depressive-like behaviors (Roque et al, 2014)

  • The collective work presented in this study is based on three evaluations regarding the effect of EE at two different developmental periods after a MS stressor: (1) behavior analysis of anxiety and depressive-like behaviors; (2) synaptic plasticity marker; and (3) peripheral hormone levels of vasopressin, oxytocin, and corticosterone

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Summary

Introduction

The maternal separation (MS) model is a well-validated rodent model that mimics early life neglect/loss in humans (Plotsky and Meaney, 1993). Mice subjected to MS from post-natal day (PND) 2 to 15 showed a decrease in time spent in the center in the open field test (OFT) as well as a decrease in the latency to immobility and an increase in total immobility time in the forced swim test (FST), suggesting increased anxiety and depressive-like behaviors (Roque et al, 2014). MS produces synaptic density decrease in young adulthood (PND 60), as measured by synaptophysin expression. Synaptophysin transiently normalizes, but a decrease in expression reappeared later in life (PND 100). This suggests that MS produces detrimental effects

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