Objective      To determine the effect of rapamycin on autistic rats and investigate the associated mechanisms.      Methods      Autistic rats were inflicted by intraperitoneal injection of sodium valproate (VPA) after pregnancy for 12.5 d. After VPA injection

pregnant rats were treated with rapamycin via oral administration at 4 mg/kg per day until weaning (in 23 d after born). There were 4 groups of newborn rats

that is

control

VPA treatment

rapamycin treatment

VPA+rapamycin treatment groups. The social interaction and neuroethology of the young rats were evaluated in 35 d after born. The levels of phosphorylated Akt-mammalian target of rapamycin (mTOR) and LC3-Ⅱ in brain tissues were detected by Western blotting. The formation of autophagosomes was observed by electron microscopy.      Results      The autistic rat mode was established successfully. Compared to control rats

the rats treated with VPA showed lower social interaction

longer moving time in central area and reduced standing time (P0.05)

which were in accordance with the typical behaviors of autistic rats. Treatment with rapamycin alone resulted in no obvious changes in the social interaction and neuroethology of young rats

but rapamycin treatment attenuatedthe VPA-induced autistic-like behaviors (P0.05). Western blotting indicated that VPA treatment enhanced the levels of p-mTOR in the brain tissues of prefrontal lobe

seahorse and cerebellum

but down-regulated the expression of LC3-Ⅱ. However

rapamycin attenuated VPA-triggered up-regulation of p-mTOR and down-regulation of LC3-Ⅱ. Electron microscopy autophagosome decreasement in the prefrontal lobe.      Conclusion      Rapamycin may improve the behaviors of autistic rats through mTOR suppression mediated autophagy enhancement.