The effect of aprepitant, a neurokinin-1 receptor antagonist, on epileptiform activity in the penicillin model of epilepsy

Abstract

Substance P (SP) is a peptide neurotransmitter that plays a role in pain transmission, stress, inflammation, and emesis through neurokinin-1 receptor (NK-1R). Previous studies of NK-1R antagonists suggest that SP can have either convulsant or anticonvulsant effects. Aprepitant, an NK-1R antagonist, is clinically used to prevent nausea and vomiting in chemotherapy and post-operative patients. However, the effects of aprepitant on epilepsy have not been studied yet. Therefore, the objective of this study was to explore the influence of aprepitant on epileptiform activity in a rat model of epilepsy induced by penicillin. Male Wistar rats, aged 2.5 to 3 months, were divided into 5 groups (n=6): Control, Vehicle, Aprepitant, Substance P, and Aprepitant+Substance P. Aprepitant was administered intragastrically (30 mg/kg) 24 hours and 3 hours before surgery. Substance P (10 pmol) was administered intraventricularly during the surgical procedure. Induction of epileptiform activity was achieved by the injection of penicillin G (500 IU) into the cortex. Electrocorticography (ECoG) recording was conducted online using the PowerLab data acquisition system for over 3 hours. The disparity in spike frequency and amplitude among groups for each 10-minute interval was assessed through One-Way ANOVA and subsequent Tukey post-hoc tests, utilizing the SPSS 15.0 software package. Epileptiform activity was observed in all rats within 3 minutes after the injection of penicillin into the cortex. No significant difference was found between groups in terms of spike frequency and amplitude. When the percentage changes in mean spike frequency and amplitude values were calculated, no significant difference was shown between the groups. Using a penicillin-induced epilepsy model, the present study showed that aprepitant does not affect epileptiform activity in the presence or absence of exogenous SP. Further studies are needed to understand possible anticonvulsant or proconvulsant properties of aprepitant.