The response to sedative doses of propofol and dexmedetomidine in a prenatal valproate autistic rat model

Introduction Autism is a challenging neurodevelopmental disorder. Previous clinical observations point to altered sedation requirements of autistic children. The current study aims to test this observation experimentally and to explore its possible mechanisms. Materials and methods Eight adult female Sprague Dawley rats were randomly divided into two groups of four each: four were injected with intraperitoneal sodium valproate on the gestational day 12.5 and four were injected with saline. On postnatal day, 28 delivered male rats were subjected to an open-field test to confirm autistic features. Then each rat was injected intraperitoneally with a single dose of propofol (50 mg/kg) or dexmedetomidine (0.2 mg/kg). Time to loss of righting reflex (LORR) and time to return of righting reflex were recorded, and on the next day, all rats were re-sedated and their electroencephalographies were recorded. Rats were killed, and hippocampal GABAA receptor gene expression and glutamate N-methyl-d-aspartate receptor gene expression were assessed. Results Autistic rats showed significantly longer time to LORR and significantly shorter time to return of righting reflex as compared with controls for both dexmedetomidine and propofol treatments (median time to LORR: 12.0 versus 5.0 for dexmedetomidine and 22.0 and 8.0 for propofol; P 0.05). Electroencephalograph showed a slow, high-amplitude wave pattern 2 min after LORR in control rats, whereas autistic ones showed a high-frequency low-amplitude awake pattern. Hippocampal GABAA receptor gene expression was significantly less in autistic rats, and N-methyl-daspartate receptor gene expression was significantly more. Conclusion The results of the current study confirm the clinical observations of increased anesthetic sedative requirements with autism and propose a mechanism for it.