Maternal separation has been used as an animal model of depression, as exposure to early-life maternal separation elicits a depressive-like phenotype in adulthood (Vetulani, 2013). Rat pups that experienced three hours of daily maternal separation from postnatal days one through 21 had reduced expression of Bdnf that corresponded with reduced H3 and H4 acetylation and increased MeCP2 binding at the Bdnf exon IV promoter within the hippocampus (Seo et al., 2016). Behaviorally, stressed animals showed increased immobility in a forced swimming test (Seo et al., 2016). These brain and behavioral outcomes were potentiated by experiencing a second stressor in adulthood (Seo et al., 2016). Similarly, GR expression was reduced with a corresponding decrease in H3 acetylation at the GR promoter and this was exacerbated by a subsequent stress incurred in adulthood (Park et al., 2017). In both studies, the implications of maternal separation on adult behavior and neurobiology were rescued by treatment with the antidepressant escitalopram (Park et al., 2017; Seo et al., 2016). These studies highlight the ability for a second stressor to potentiate the effects of early-life stress and could offer a potential mechanism through which early stress could predispose an individual to depression.
