Environmental enrichment has minimal effects on behavior in the Shank3 complete knockout model of autism spectrum disorder

INTRODUCTION: Several studies have supported the use of enriched environments to prevent the manifestation of ASD‐like phenotypes in laboratory rodents. While the translational value of such experiments is unknown, the findings have been relatively consistent across many different models. METHODS: In the current study, we tested the effects of early environmental enrichment on a mouse model of ASD with high construct validity, the Shank3 ∆e4–22 mice our laboratory previously generated and characterized. RESULTS: Contrary to previous reports, we found no benefits of enriched rearing, including no change in repetitive self‐grooming or hole‐board exploration. Instead, we found that early environmental enrichment increased anxiety‐like behavior in all mice regardless of genotype and decreased motor performance specifically in wild‐type mice. CONCLUSIONS: Although using a different enrichment protocol may have rescued the phenotypes in our mouse model, these results suggest that a “one‐size fits all” approach may not be the best when it comes to behavioral intervention for ASD and underscores the need for effective pharmaceutical development in certain genetic syndromes with severe symptom presentation.