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

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 microM) 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 microM) 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 microg/kg (e.g. 350 microg/kg). Lower doses of alfentanil (25 microg/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 mu-receptor opioids in chronic temporal lobe epilepsy.

Physical training reverts hippocampal electrophysiological changes in rats submitted to the pilocarpine model of epilepsy.

Physical exercise and fitness programs in patients with epilepsy are still a matter of controversy. Effects of physical exercise in animals with epilepsy have been demonstrated. To further investigate the possible mechanisms by which physical activity interferes with epileptogenesis, the present work was aimed to study the effect of aerobic exercise on "in vitro" hippocampal electrophysiological parameters observed in rats submitted to the pilocarpine model of epilepsy. Electrophysiological changes were monitored by extracellular field potentials recorded from CA1 area. Control rats and rats with epilepsy were submitted to an aerobic exercise program. The number of population spikes (PS) and slope of field excitatory postsynaptic potentials (fEPSP) were analyzed. Trained rats with epilepsy exhibited a reduction in PS when compared with nontrained rats with epilepsy in different concentrations of extracellular potassium or bicuculline. Physical training also enhanced the late phase of LTP in rats with epilepsy. Our results indicate that physical training reduces CA1 hyperresponsiveness and can modify synaptic plasticity in rats submitted to the pilocarpine model of limbic epilepsy.

Intrastriatal methylmalonic acid administration induces convulsions and TBARS production, and alters Na+,K+-ATPase activity in the rat striatum and cerebral cortex.

PURPOSE: Methylmalonic acid (MMA) inhibits succinate dehydrogenase (SDH) and beta-hydroxybutyrate dehydrogenase activity in vitro. Acute intrastriatal administration of MMA induces convulsions through glutamatergic mechanisms probably involving primary adenosine triphosphate (ATP) depletion and free radical generation. In this study we investigated whether the intrastriatal administration of MMA causes lipoperoxidation and alteration in Na+, K+-ATPase activity ex vivo and characterized the electrographic changes elicited by the intrastriatal administration of this organic acid. METHODS: MMA-induced lipoperoxidation, alterations in Na+, K+-ATPase activity and electrographic changes were measured by measuring total thiobarbituric acid-reacting substances and inorganic phosphate release by spectrophotometry, and by depth electrode recording, respectively. RESULTS: We demonstrated that intrastriatal MMA (6 mmol) injection causes convulsive behavior and electrographically recorded convulsions that last approximately 2 h. Concomitant with the increase of thiobarbituric acid-reacting substances (TBARS) content, we observed a significant inhibition of Na+,K+-ATPase activity in the striatum, and activation of Na+,K+-ATPase activity in the ipsilateral cerebral cortex. Intrastriatal MMA injection increased the content of TBARS in the striatum measured 30 min (32.4 +/- 12.0%, compared with the noninjected contralateral striatum) and 3 h (39.7 +/- 5.1%, compared with the noninjected contralateral striatum) after MMA injection. TBARS content of the ipsilateral cerebral cortex increased after MMA injection at 30 min (42.1 +/- 6.0%) and 3 h (40.4 +/- 20.2%), and Na+,K+-ATPase activity in the ipsilateral cerebral cortex increased during ictal activity (113.8 +/- 18%) and returned to basal levels as electrographic convulsions vanished in the cortex. Interestingly, intrastriatal MMA administration induced a persistent decrease in Na+,K+-ATPase activity only in the injected striatum (44.9 +/- 8.1% at 30 min and 68.7 +/- 9.4 at 3 h). CONCLUSIONS: These data suggest that MMA induces lipoperoxidation associated with Na+,K+-ATPase inhibition or activation, depending on the cerebral structure analyzed. It is suggested that Na+,K+-ATPase inhibition may play a primary role in generating MMA-induced convulsions.