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Environmental enrichment is a powerful way to stimulate brain and behavioral plasticity. However the required exposure duration to reach such changes has not been substantially analyzed. We aimed to assess the time-course of appearance of the beneficial effects of enriched environment. Thus, different behavioral tests and neurobiological parameters (such as neurogenesis, brain monoamines levels, and stress-related hormones) were concomitantly realized after different durations of enriched environment (24 h, 1, 3, or 5 weeks). While short enrichment exposure (24 h) was sufficient to improve object recognition memory performances, a 3-week exposure was required to improve aversive stimulus-based memory performances and to reduce anxiety-like behavior; effects that were not observed with longer duration. The onset of behavioral changes after a 3-week exposure might be supported by higher serotonin levels in the frontal cortex, but seems independent of neurogenesis phenomenon. Additionally, the benefit of 3-week exposure on memory was not observed 3 weeks after cessation of enrichment. Thus, the 3-week exposure appears as an optimal duration in order to induce the most significant behavioral effects and to assess the underlying mechanisms. Altogether, these results suggest that the duration of exposure is a keystone of the beneficial behavioral and neurobiological effects of environmental enrichment.

Environmental Enrichment Duration Differentially Affects Behavior and Neuroplasticity in Adult Mice