Environmental enrichment (EE) is known to have an anxiolytic effect in several animal models; however, the molecular mechanisms underlying these behavioral changes are not understood. In this study, we have shown that the anxiolytic effect of EE is associated with alterations in the corticotropin-releasing factor receptor type 1 (CRFR1) expression levels in the limbic system. We found that the decrease in anxiety-like behavior after housing in enriched conditions was associated with very low levels of CRFR1 mRNA expression in the basolateral amygdala of C57BL/6 mice. We further showed using a lentiviral-based system of RNA interference, that knockdown of CRFR1 mRNA expression in the basolateral amygdala induces a significant decrease in anxiety levels, similar to those achieved by EE nurture. Our data strongly suggest that reduced expression of CRFR1 mRNA levels in the basolateral amygdala mediates the effect of EE on anxiety-like behavior.