Distinct effects of resveratrol on seizures and hyperexcitability induced by NMDA and 4-aminopyridine

Objectives: The antiepileptic activity of resveratrol has been revealed in various experimental models of epilepsy. The present study evaluated the effects of resveratrol on the seizures and hyperexcitable neuronal activity associated with activation of N-methyl-d-aspartic acid (NMDA) receptor and inhibition of voltage-gated potassium channels.Methods: The effects of resveratrol on seizure thresholds, excitatory field potentials (EFPs) and action potentials induced by NMDA and 4-aminopyridine (4-AP) were monitored in mice, the mouse cortical slices and rat cortical neurons, respectively.Results: Resveratrol increased the NMDA-induced seizure thresholds and suppressed the frequency of NMDA/glycine-evoked EFPs and action potentials. However, resveratrol lowered the 4-AP-induced thresholds for myoclonic twitch and face and forelimb clonus, yet enhanced the thresholds for running and bouncing clonus and tonic hindlimb extension at the higher dose (50 mg/kg). A similar biphasic response of resveratrol was observed in the frequency of EFPs and action potential firings evoked by 4-AP, with enhancement at lower concentrations, but suppression at higher concentrations.Discussion: These findings suggest that resveratrol might be capable of protecting against the seizure types related to neuronal excitability and progression mediated by NMDA receptor activation, but not suitable for the seizures caused by disturbance of the voltage-dependent potassium channels.