Exaggerated fear conditioning memory and increased amygdala cell density in the valproic acid animal model of autism Nikfarjam H1*, Moghimi A1, Hosseini M2, Mahdavi-shahri N1, Edalatmanesh MA3, Vafaee F2 1. Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, 2. Neuroscience Research Center and Department of Physiology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran 3. Department of Physiology, Science & Research Branch, Islamic Azad University, Fars, Iran. n.nikfarjam@gmail.com Intruduction: Maternal valproic acid (VPA) exposure is capable of inducing experimental autism resulting in neurobehavioral aberrations. Autism is characterized with impairments in social interactions, as well as stereotyped, repetitive patterns of behaviors and interests. Previous studies on the VPA model of autism indicate that the amygdala is hyper-reactive, hyper-plastic and mediates hyper-fear, excessive fear memory generalization, and resistance to fear extinction. Thus, we investigated the microanatomical effects of VPA on amygdala and fear conditioning memory in juvenile and adult rat model of autism. Methods: We used the VPA rat model of autism to screen for autism-like symptoms in rats such as postnatal physical development, social behavior, stereotyped-repetitive behaviors and movements, nociception and tactile threshold and anxiety as well as passive avoidance test for alterations in amygdala-dependent fear processing, and evaluate neuronal density in amygdala by means of histopathological studies. Results: VPA-exposed offsprings showed delayed physical development, dysfunctional social behavior, increased nociception threshold, hyperlocomotor activity, and anxiety. Furthermore, VPA-treated pups were more anxious and exhibited abnormally high and longer lasting fear memories. Animals were sacrificed on postnatal day 65 and brain was subjected to histopathological examination. Histological findings confirm that the neuronal density in amygdala was increased. Conclusion: We show exaggerated fear memories in an animal model of autism with hyper cell density in amygdala. This study provides further evidence to support the notion that the fear memory correlated to amygdala cell density is highly increased in this animal model of autism. Key words: Autism, Valproic acid, Amygdala, Fear conditioning memory, Cell density.

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