THE EFFICACY OF LACOSAMIDE AND PERAMPANEL IN THE ANIMAL MODEL OF AUTISM SPECTRUM DISORDER

Abstract Background Autism spectrum disorders (ASD) are pervasive developmental disorders characterized by social deficits and restrictive patterns of behavior and interests. Epilepsy is comorbidity in ASD patients. The imbalance of excitation and inhibition in neural circuitry is hypothesized for the pathophysiology of ASD as well as epilepsy. It is epidemiologically reported that administration of valproic acid (VPA) during pregnancy increases the risk of ASD in the offspring. In this study, we investigated therapeutic potential of anti-epileptic drugs for ASD using prenatal VPA-induced ASD animal model. Methods Pregnant mice were injected with VPA (500 mg/kg, i.p.) on gestational day 12. The offspring were subjected social interaction test, novel object recognition and repetitive behavior test. The offspring were injected with anti-epileptic drugs (lacosamide, and perampanel) before each behavioral test. Result The offsprings from mice exposed to VPA during pregnancy showed decrease in social interaction time and exploratory preference for novel object, and increase in grooming numbers. The lacosamide, and perampanel increased exploratory preference for novel object and decreased grooming numbers in the offsprings from mice exposed to VPA during pregnancy. Conclusion Behavioral changes in offsprings from mice exposed to VPA during pregnancy are associated with the symptom of ASD (decrease in social interaction time: social disability, decrease in approach time for novel object: cognitive dysfunction). We suggest that lacosamide and perampanel improve visual recognition memory impairment and increased repetitive behavior in ASD model mice. These data suggested that anti-epileptic drugs attenuated could have therapeutic potential for ASD symptoms.