Environmental enrichment partially rescues neurodevelopmental milestone delays in the prenatal VPA rat model of autism spectrum disorders.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by early sensorimotor delays, which often precede core social deficits as well as restricted and repetitive behaviors. Environmental enrichment (EE) is a promising behavioral intervention for ASD; however, its potential to prevent these earliest neurodevelopmental disruptions remains unexplored. This study investigated whether sustained EE could prevent early milestone delays in a prenatal valproic acid (VPA) rat model of ASD. Female Wistar rats were housed in standard (SH) or EE conditions for eight weeks, beginning two weeks before conception and continuing through lactation. Dams received a single injection of VPA (500 mg/kg) or saline on gestational day 12.5. Offspring were assessed daily from postnatal day (PND) 1-21 for the acquisition of physical and sensorimotor milestones. EE significantly mitigated VPA-induced delays in a subset of key neurodevelopmental milestones. While EE did not fully normalize development to control levels, a composite neurodevelopmental score revealed that EE significantly attenuated the global impairment induced by VPA. These findings demonstrate that preconception-perinatal EE confers partial protection against functional neurodevelopmental deficits in a predictive ASD model, highlighting its potential as a preventive strategy targeting the earliest manifestations of neurodevelopmental disruption.