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

Abstract

IntroductionEpileptogenesis 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.MethodsFemale 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.ResultsFor 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.ConclusionsThe results suggest that adequate doses of lamotrigine can prevent seizure development in the pentylenetetrazole kindling rat model.

Neuroprotective Effect of Fisetin Through Suppression of IL-1R/TLR Axis and Apoptosis in Pentylenetetrazole-Induced Kindling in Mice

“…Neuronal damage associated with PTZ-induced kindling may be a possible consequence of recurrent seizure activity ( 60 ). In this study, histopathological results from Nissl staining showed significant neuronal damage in the CA1 area in the PTZ group, which is in agreement with previous studies ( 61 , 62 ). However, fisetin administration provided significant protection against hippocampal neuronal damage in a dose-dependent manner.…”

“…staining showed significant neuronal damage in the CA1 area in the PTZ group, which is in agreement with previous studies (61,62). However, fisetin administration provided significant protection against hippocampal neuronal damage in a dose-dependent manner.…”

The effects of lamotrigine and ethosuximide on seizure frequency, neuronal loss, and astrogliosis in a model of temporal-lobe epilepsy

“…Our results with LTG are difficult to be compared with those achieved by kindling models of TLE, and in some studies (Stratton et al, 2003;Chen et al, 2017), antiepileptogenesis or disease modifying effects were suggested. However, in the kindling models, LTG has been administered immediately prior to the electrical or chemical kindling sessions (Stratton et al, 2003;Postma et al, 2000;Chen et al, 2017), therefore, antiepileptic effects were evaluated.…”

“…Our results with LTG are difficult to be compared with those achieved by kindling models of TLE, and in some studies (Stratton et al, 2003;Chen et al, 2017), antiepileptogenesis or disease modifying effects were suggested. However, in the kindling models, LTG has been administered immediately prior to the electrical or chemical kindling sessions (Stratton et al, 2003;Postma et al, 2000;Chen et al, 2017), therefore, antiepileptic effects were evaluated. Sometimes antiepileptogenic effects were suggested based on the results obtained after a wash-out period, however, they might be fully or partly explained by an antiepileptic action since the intensity of the kindled seizures might be less (curtailing) due to the administration of LTG prior to kindling; consequently, epileptogenesis might be slower.…”

“…Older and newer anti-epileptic medications, including lamotrigine (LTG), have been investigated for their antiepileptogenic or disease modifying and neuroprotective effects in a variety of TLE models with different results. LTG demonstrated antiepileptogenic-like effects by blocking seizure development during treatment period in a rat amygdala (Stratton et al, 2003) and PTZ kindling model (Chen et al, 2017). However, LTG was given in both studies prior to the daily kindling sessions and this may have curtailed the intensity and duration of the after discharge (AD); as a consequence, this might have slowed down epileptogenesis.…”