Adverse experiences early in life may sensitize the hippocampus to subsequent stressors throughout the individual's life. We analyzed in male rats, whether, the interaction between early maternal separation and chronic stress affects: (1) the volume of the dorsal hippocampus, (2) CA1, CA2/3 and dentate gyrus (DG) and (3) hippocampal-dependent memory in adulthood. Male Wistar rats were subjected to daily maternal separation for 4.5 h between postnatal days 1-21. From postnatal day 50, animals were exposed to a chronic unpredictable stress paradigm during 24 days. The volumes of the dorsal hippocampus, their areas or strata did not reveal significant differences between treatments. Non-maternally separated and stressed animals showed poor hippocampal performance in a contextual fear conditioning test, with a significant reduction in freezing behavior during post-conditioning compared with control and maternally separated and stressed animals. Also, memory retrieval 24 h after conditioning was significantly weaker in this group than in control animals. Memory performance in maternally separated and stressed rats was similar to control animals. Our results show an interaction between early environment experiences and chronic variable stress in young adulthood as evidence that early stressful experiences do not necessarily lead to a negative outcome but can help in maintaining brain plasticity and increase fitness when animals reach adulthood.

Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

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