Embryological exposure to valproic acid induces social interaction deficits in zebrafish (Danio rerio): A developmental behavior analysis

Changes in social behavior are associated with brain disorders, including mood disorders, stress, schizophrenia, Alzheimer's disease, and autism spectrum disorders (ASD). Autism is a complex neurodevelopmental disorder characterized by deficits in social interaction, impaired communication, anxiety, hyperactivity, and the presence of restricted interests. Zebrafish is one of the most social vertebrates used as a model in biomedical research, contributing to an understanding of the mechanisms that underlie social behavior. Valproic acid (VPA) is used as an anti-epileptic drug,and mood stabilizer; however, prenatal VPA exposure in humans has been associated with an increased incidence of autism and it can also affect fetal brain development. Therefore, we conducted a behavioral screening at different periods of zebrafish development at 6, 30, 70, and 120 dpf (days postfertilization) after VPA exposure in the early development stage to investigate social behavior, locomotion, aggression, and anxiety. VPA (48 mu M) exposure during the first 48 hpf (hours postfertilization) did not promote changes on survival, morphology, and hatching rate at 24 hpf, 48 hpf, and 72 hpf. The behavioral patterns suggest that VPA exposure induces changes in locomotor activity and anxiety at different developmental periods in zebrafish. Furthermore, a social interaction deficit is present at 70 dpf and 120 dpf. VPA exposure did not affect aggression in the adult stage at 70 dpf and 120 dpf. This is the first study that demonstrated zebrafish exposed to VPA during the first 48 h of development exhibit deficits in social interaction, anxiety, and hyperactivity at different developmental periods. (C) 2015 Elsevier Inc. All rights reserved.