The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb/C mice

•Pro-neurogenic effects of environmental enrichment (ENR) persist after cessation.•ENR cessation does not decrease doublecortin-positive cells in six-month-old mice.•ENR induces behavioral protection against chronic mild stress. Because stress may underlie the presence of depressive episodes, strategies to produce protection against or to reverse the effects of stress on neuroplasticity and behavior are relevant. Preclinical studies showed that exposure to stimuli, such as physical activity and environmental enrichment (ENR), produce beneficial effects against stress causing antidepressant-like effects in rodents. Additionally, ENR induces positive effects on neuroplasticity, neurochemistry and behavior at any age of rodents tested. Here, we analyzed whether ENR exposure prevents the development of depressive-like behavior produced by unpredictable, chronic mild stress (CMS) exposure as well as changes in hippocampal neurogenesis in a six-month-old female Balb/C mice, strain that shows low baseline levels of hippocampal neurogenesis. Mice were assigned to one of four groups: (1) normal housing-normal housing (NH-NH), (2) NH-CMS, (3) ENR-NH, or (4) ENR-CMS. The animals were exposed over 46 days to ENR or NH and subsequently to NH or CMS for 4 weeks. ENR induces long-term effects protecting against CMS induction of anhedonia and hopelessness behaviors. Independent of housing conditions, ENR increased the number of proliferative cells (Ki67), and CMS decreased the number of proliferative cells. ENR increased the newborn cells (BrdU) and mature phenotypes of neurons; these effects were not changed by CMS exposure. Similarly, the number of doublecortin-positive cells was not affected by CMS in ENR mice, which showed more cells with complex dendrite arborizations. Our study suggests that ENR induces protection against the effects of CMS on behavior and neuroplasticity in six-month-old Balb/C mice.