276. The efficacy of low-dose lacosamide and perampanel in attenuating autism spectrum disorders-like behaviors in mice exposed to prenatal valproic acid

Abstract

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 neural excitation and inhibition is hypothesized for the pathophysiology of ASD as well as epilepsy. Lacosamide and perampanel are the new third-generation anti-seizure medications used for focal epilepsy. But it remains unclear whether these antiepileptic drugs that correct the balance between neural excitation and inhibition improve ASD symptoms. Aims & Objectives 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 lacosamide and perampanel for ASD in mice exposed to prenatal VPA. Method Pregnant mice were injected with VPA (500 mg/kg, i.p.) on gestational day 12. The offspring were subjected to social interaction test, novel object recognition test and repetitive behavior test. Lacosamide (1-15 mg/kg, i.p.) and perampanel (0.1-1.5 mg/kg, i.p.) were treated before each behavioral test. The mRNA expression levels of SCN2A, SCN4B and Arc in the prefrontal cortex were measured by real-time PCR. Results The mice exposed to prenatal VPA showed decrease in social interaction time and exploratory preference for novel object and increase in numbers grooming associated with increase of SCN2A, SCN4B and Arc mRNA levels in the prefrontal cortex. The lacosamide (1mg/kg), and perampanel (0.1mg/kg) attenuated these behavioral changes and decreased Arc mRNA expression levels in mice exposed to prenatal VPA. Discussion & Conclusions Behavioral changes in mice exposed to prenatal VPA were resembled symptoms of ASD. Increased levels of SCN2A, SCN4B, and Arc suggested hyper-excitability in the prefrontal cortex of mice exposed to prenatal VPA. The attenuation effect of lacosamide and perampanel at low doses on the ASD-like behaviors and hyper-excitability suggested that these antiepileptic drugs have therapeutic potential for treating ASD symptoms.