Introduction: Autism is characterized by behavioral impairments in three main domains: social interaction; language, communication and imaginative play; and range of interests and activities. However, Recent studies have suggested that hyper-perception, hyper-attention, and hyper-memory, which may lie at the heart of most autistic symptoms. Methods: Pregnant Wistar rats were administered either valproic acid (VPA, 400 mg/kg) or saline during fetal neural tube development on embryonic day (ED) 12.5. The present study examined postnatal physical development, social behavior, stereotyped-repetitive behaviors and movements, nociception threshold and exploratory activities as well as spatial memory. Stereological analyses of cells in five regions of the hippocampus, a structure involved in spatial memory, were done to determine neuronal density in both groups. Results: A single intra-peritoneal injection of VPA to pregnant rats has been shown to produce severe autistic-like symptoms in the offspring. The results showed significant delayed physical maturation, behavioral impairments such as a lower tendency to initiate social interactions, lower exploratory activities, increase of repetitive behaviors and increased nociception threshold in juvenile and adult rats. Spatial learning and memory also enhanced in the Morris water maze test. Furthermore, histological analysis demonstrated that the neuronal density in five separate regions of hippocampus (CA1, CA2, CA3, Dentate gyrus and Subiculum) were increased on postnatal day 60. Conclusion: This Study shown that early embryonic exposure to VPA was a good animal model for further analysis of hippocampal neuroanatomical alterations in autism. Our results also suggest that increased cell density of hippocampus may lead to enhanced spatial memory of rats prenatally exposed to VPA.

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