Abstract: Objective To test the effect of sulindac on autistic behaviors in a rat model and explore the possible mechanisms.
Methods Autistic rat models were established by a single intraperitoneal injection of sodium valproate (VPA) at 12.5 days of
pregnancy. The pregnant rats were treated with oral sulindac at a daily dose of 80 mg/kg until weaning of the newborn rats (23
days after being born), which were divided into control, VPA treatment, sulindac treatment, and VPA+ sulindac treatment
groups. The social interaction and neuroethology of the newborn rats were evaluated at 35 days, and the levels of β-catenin
and phosphorylated Gsk3β in the brain tissues were investigated by Western blotting. Results Compared with the control rats,
the rats treated with VPA showed lower social interaction, longer moving time in central area, and reduced standing times.
Treatment with sulindac alone resulted in no obvious changes in the social interaction or neuroethology of the newborn rats,
but sulindac treatment corrected VPA-induced autistic-like behaviors. Sulindac also attenuated VPA-triggered p-Gsk3β
downregulation and β-catenin upregulation in the prefrontal lobe, seahorse and cerebellum. Conclusion Sulindac can improve
the behaviors of autistic rats possibly by suppressing Wnt signaling pathway.