Hyperactivation of the amygdala correlates with impaired social play behavior of prepubertal male rats in a maternal immune activation model.

Maternal infection during pregnancy is an environmental risk factor for neurodevelopmental dysfunction, such as autism spectrum disorder (ASD). This study investigated the effect of maternal immune activation (MIA) on the behavior profile of prepubertal offspring and whether MIA alters the neuronal activation pattern of brain areas related to social play behavior. Pregnant Wistar rats received 500 µg/kg of lipopolysaccharide or saline solution on gestational day 16. Their offspring were tested using behavioral tasks to capture some of the core and associated ASD-like symptoms. Neuronal activation, indexed via c-fos expression after social play behavior, was evaluated in several brain areas. MIA had a number of adverse effects on dams and reduced the number of successful births and litter size. MIA induced sex-specific autistic-like features by a reduction in ultrasonic vocalizations in response to separation from the mother and nest, reduction in discrimination between neutral odors and their nest odor, moderate effect in stereotypies in the hole-board test, impaired risk assessment phenotype, and reduction in social play behavior without changes in locomotor activity only in prepubertal male offspring. A decrease in social play behavior may be associated with a decrease in the number of c-fos-positive cells in the prefrontal cortex and striatum, but hyperactivation of the basolateral and basomedial amygdala. Prenatal immune challenge results in ASD-like symptoms such as impaired risk assessment behavior, communication, and social interactions in male prepubertal offspring. Impaired social play behavior is correlated with neuronal hyperactivation in the amygdala.