Pro-epileptic effect of alfentanil in rats subjected to pilocarpine-induced chronic epilepsy

Abstract

Pharmacological induction of epileptiform activity is a complementary method to study the epileptogenic area in drug-resistant epileptic patients. Among the different activation methods, fentanyl derivatives (e.g. alfentanil) provide one of the most efficient tools in triggering epileptiform abnormalities in surgical candidates. In this study, we tested the pro-epileptic effect of different concentrations of alfentanil in hippocampal slices obtained from control and pilocarpine-treated chronic epileptic rats. The pro-convulsant action of alfentanil was also studied in control and pilocarpine-treated epileptic rats implanted with subdural and hippocampal electrodes for electroencephalographic recordings. In 90% of slices from control animals, application of alfentanil (0.1–5 μM) induced a significant enhancement in amplitude and number of population spikes recorded in the hippocampal CA1 region. In contrast, alfentanil produced a significant reduction in the amplitude of population spikes in slices from pilocarpine-treated epileptic rats. These changes were accompanied by a significant increase in the number of population spikes in the form of epileptiform multispike responses of epileptic slices. Naloxone (20 μM) antagonized the effect of alfentanil in both control and epileptic slices, reducing the number of population spikes in slices from epileptic rats. In control rats, alfentanil induced epileptiform abnormalities in the hippocampal and cortical electroencephalographic recordings but only at concentrations higher than 200 μg/kg (e.g. 350 μg/kg). Lower doses of alfentanil (25 μg/kg) elicited epileptiform abnormalities only in chronic epileptic rats. The potent action of a minimal dose of alfentanil in inducing epileptiform activity suggests an enhancement of the pro-convulsant action of μ-receptor opioids in chronic temporal lobe epilepsy.