Abstracts

Rationale: The maximal electroshock seizure (MES) and pentylenetetrazole (PTZ) seizure tests are widely used models to screen drugs for anticonvulsant activity. Recently, Blanco et al. (Epilepsia, 50 (4):824-831, 2009) reported that several clinically established antiepileptic drugs (AEDs), including phenobarbital (PB), lost their anticonvulsant effect on PTZ-induced seizures, but not MES, when these tests were performed in rats that had developed epilepsy after a pilocarpine-induced status epilepticus (SE). The authors suggested that the PTZ test in animals pretreated with pilocarpine might constitute an effective and valuable method to screen AEDs. The aim of our study was to test whether similar results are obtained with the PTZ and MES tests in mice following a pilocarpine-induced SE.Methods: We used the pilocarpine model to induce SE in female NMRI mice. Six weeks after SE, we determined the seizure threshold either by the timed i.v. PTZ seizure threshold test or the MES threshold (MEST) test in epileptic (PTZ n=22; MEST n=26) and control mice (PTZ n=20; MEST n=19). The threshold for PTZ seizures was calculated in mg/kg PTZ for the first myoclonic twitch by infusion of a 1% PTZ solution into the tail vein of freely moving mice. The MEST was calculated as the median convulsive current (CC₅₀) that induced seizures in 50% of the mice tested, using a sine-wave alternating current via corneal electrodes and taking tonic hindlimb extension as seizure. In parallel, a group of naive NMRI mice (n=40) was used to determine the i.p. dose of PB for a seizure threshold increase of approximately 40-50% in the PTZ threshold test and MEST, respectively. Respective doses were 18 mg/kg for the PTZ test and 10 mg/kg for the MEST, respectively. Seven weeks after SE, these doses of PB were tested with a pretreatment time of 30 minutes in both seizure threshold tests in epileptic and control mice.Results: Six weeks after SE, mean seizure thresholds in epileptic and control mice did not differ significantly in the PTZ test (44.77 mg/kg and 47.17 mg/kg PTZ) and the MEST (CC₅₀=16.92 mA and CC₅₀=16.79 mA), respectively. Furthermore, the effect of PB on seizure thresholds was not different between controls and epileptic mice. PB increased the seizure threshold by 36% in control and 39% in epileptic mice in the MEST and by 32% and 40% in the PTZ test, respectively.Conclusions: We tested PB in the PTZ and MEST model in mice and found comparable anticonvulsant efficacy of this AED in epileptic and control mice. In apparent contrast to the results of Blanco et al. (2009) in rats, our study demonstrates that, at least with PB, epileptic mice do not show a different response profile in the PTZ and MEST models of acute seizures compared to non-epileptic control mice. Testing of further AEDs is under way.