Objectives: 

Rapid Kindling with Recurrent Hippocampal Seizures (RKRHS) can result in a rapidly developing, transient fully kindled state or a slowly developing, permanent fully kindled state respectively. This study assesses the use of RKRHS in drug testing by investigating the anti-epileptic and anti-epileptogenic profile of LEV.

Methods: 

Wistar rats were implanted with a stimulation electrode in the right hippocampus and several recording electrodes. One week later, rats received 12 stimulations a day (RKRHS) for several consecutive or alternating days, until they were fully kindled. In the anti-epileptic test procedure, rats fully kindled according to the serial day protocol were randomly assigned to an active (n = 8) and a control (n = 6) group and injected (intraperitoneal, i.p.) with LEV (54 mg/kg) or saline (0.9% NaCl) respectively. One hour later, rats received additional kindling stimulations, during which the effect of LEV on seizure semiotics and afterdischarge duration was assessed. In the anti-epileptogenic testing procedure, rats fully kindled using the alternate day protocol were randomly assigned to an active (n = 10) and a control (n = 5) group and implanted with an osmotic minipump containing either LEV (500 mg/ml) or saline (0.9% NaCl). After one week of treatment, rats were retested for their kindled state.

Results: 

In the anti-epileptic testing procedure, mean seizure stage dropped to 1.7 ± 1 one hour after injection of LEV (54 mg/kg), compared to 4.5 ± 1 in controls (p < 0.05). Mean ADD was also significantly shorter in the active group than in controls; 21.2 s ± 5.0 s versus 57.2 s ± 8.2 s respectively (p < 0.05). These effects showed a time-dependant decline but stayed significant for at least 2.5 h following LEV administration. Results from the anti-epileptogenic test showed a significant influence of LEV on seizure characteristics only during the first retest stimulation: seizure score was reduced from 4.2 ± 0.8 to 2.1 ± 0.8 compared to controls, while ADD showed a decline from 93.0 s ± 42.5 s to 40.2 s ± 27.1 s (p < 0.05).

Discussion: 

In the anti-epileptic testing procedure, serial day RKRHS proved to be a useful model allowing fast assessment of the efficacy of anti-epileptic drugs against kindled seizures. LEV displayed potent anti-epileptic activity in serial day RKRHS but the anti-epileptogenic testing procedure revealed only a small but significant effect, indicating that chronic LEV treatment might elevate the seizure threshold.