Khadijeh Mirzaee Khoram-Abadi - Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
Sara Haratizadeh - Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
Mohsen Basiri - Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
Mahdieh Parvan - Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran
Fahimeh Pourjafari - Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
Iraj Aghaei - Neuroscience Research Center, Guilan University of Medical Sciences, Rasht, Iran
Sedigheh Amiresmaili - Department of Physiology, Bam University of Medical Sciences, Kerman, Iran
Masoumh Nozari - Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Objective(s): Due to the crucial role of polyamines during fetal growth and development, we aimed to determine the effect of prenatal administration of agmatine, an endogenous active metabolite of arginine, and a nutritional supplement, on autistic-like behaviors, oxidative-anti-oxidative profile, and histopathological changes of the prefrontal cortex (PFC) and CA۱ area of the hippocampus in valproic acid (VPA) model of autism in male rats. Materials and Methods: VPA was injected intraperitoneally on embryonic days (ED) ۱۲.۵, and the pregnant rats were gavaged with agmatine between E۶.۵ to E۱۸.۵ (۱۳ days), at doses of ۰.۰۰۱, ۰.۰۱, and ۰.۱ mg/kg. The autism-like behaviors and memory of male pups were analyzed via open-field, three-chamber, and novel object recognition tests. Serum oxidative stress and the histological changes in the PFC and CA۱ were assessed at the end of the study. Results: The results suggest that prenatal agmatine reduced autistic-like behaviors by decreasing cell loss in CA۱ and PFC. We observed no alterations in superoxide dismutase (SOD) level and total anti-oxidant capacity (TAC) between groups. VPA decreased catalase (CAT) activities, while agmatine decreased malondialdehyde (MDA) activity. Conclusion: Overall, this investigation suggests that agmatine may be a potential candidate for the early treatment and even prevention of appearance of autism symptoms.

Agmatine, Autism, Behavior, pregnancy, Rat, Valproic acid