Behavioral Outcomes of Valproic Acid Exposure in Zebrafish: Evaluating Autism-Related Traits

Autism spectrum disorder (ASD) is a complex neurodevelopmental disability with multifactorial causes, including genetic, epigenetic, and environmental factors. Valproic acid (VPA) is an antiepileptic widely studied as a risk factor for ASD. Maternal use of VPA during pregnancy increases the risk of ASD in the offspring. Additionally, VPA is frequently used to model ASD in animals and induce ASD-like behavior in zebrafish. This thesis aimed both to investigate the effects of VPA exposure as a risk factor and to establish a protocol for a drug-induced zebrafish model of ASD. To do so, zebrafish embryos at 10 hours post-fertilization (hpf) were exposed to VPA for 48 hours to form three groups: a high-dose group (25μM, HG), a low-dose group (12.5μM, LG), and a control group (CG). At 28 days post-fertilization (dpf), 66 zebrafish underwent two behavioral assays: a social preference test and a light-dark preference test, the latter being an indicator of anxiety-like behavior. A one-way ANOVA revealed no significant difference between the three groups for the social preference test. However, unexpectedly, HG crossed the light-dark barrier significantly more than LG and CG. Although the results contradict our hypothesis, the significant result in HG indicated potential hyperexcitability, supporting further investigation into VPA’s risk and effects.