Effect of lamotrigine on seizure development in a rat pentylenetetrazole kindling model

Epileptogenesis is a process of seizure development. Lamotrigine is a novel antiepileptic drug which is also used for antiepileptogenic research. Kindling models are recommended as potentially useful tools for antiepileptogenic treatment discovery. However, previous studies demonstrated that the antiepileptogenic effect of lamotrigine is controversial in the electrical kindling model. Chemical kindling such as with pentylenetetrazole is another kindling model. The aims of this study were to examine whether lamotrigine could prevent the development of seizure in pentylenetetrazole kindling rats.

Female rats were kindled by subconvulsive doses of pentylenetetrazole (35 mg/kg) once every other day for 15 times. Thereafter, the kindled rats received different doses of lamotrigine (5, 10 and 20 mg/kg) before pentylenetetrazole to observe the anticonvulsant effect. For the antiepileptogenic experiment, rats were kindled as the same way while pretreated (1 h) with different doses of lamotrigine (5, 10 and 20 mg/kg) before each injection of pentylenetetrazole. After a washout period for 1 week, the rats were administrated with pentylenetetrazole again for 3 times. The seizures were recorded each time. Later it was in vivo electrophysiological experiments followed with histologic analysis.

For the anticonvulsant experiment lamotrigine dose-dependently suppressed pentylenetetrazole-induced seizures. Here, 20 mg/kg of lamotrigine pretreatment significantly blocked the seizure development in rats for their seizure stages remained longer in 1-3 during the kindling phase. Mean seizure stages or generalized seizure durations in the 10 and 20 mg/kg lamotrigine pretreated groups were significantly lower or shorter when received 3 times of pentylenetetrazole after the washout period. Electrophysiological study also demonstrated 20 mg/kg of lamotrigine pretreatment obviously eliminated increased population spike amplitude in hippocampus. However, different doses of lamotrigine pretreatment could not alleviate severity of hippocampal neuronal damage.

The results suggest that adequate doses of lamotrigine can prevent seizure development in the pentylenetetrazole kindling rat model.