University of Catanzaro, School of Medicine, Science of Health Department, Catanzaro, Italy.
University of Catanzaro, School of Medicine, Science of Health Department, Catanzaro, Italy; CNR, Institute of Neurological Sciences, Pharmacology Section, Roccelletta di Borgia, Catanzaro, Italy.
Pharmacol Rep. 2019 Oct;71(5):833-838. doi: 10.1016/j.pharep.2019.04.017. Epub 2019 Apr 24.
WAG/Rij rats represent a validated genetic animal model of epileptogenesis, absence epilepsy and depressive-like comorbidity. Some treatments (e.g. ethosuximide), using specific protocols, prevent the development of spontaneous absence seizures. Accordingly, ethosuximide increases remission occurrence in children with childhood absence epilepsy in comparison to valproic acid. Considering that in this animal model, antiepileptogenic effects are, in some cases, not retained over time, we studied whether the antiepileptogenic effects of both ethosuximide and levetiracetam (which also possesses antiepileptogenic effects in this and other animal epilepsy models) would be retained 5 months after drug suspension.
WAG/Rij rats of ˜1 month of age were treated long-term with one of the two drugs at a dose of ˜80 mg/kg/day for 17 consecutive weeks; 1 and 5 months after drug suspension, the development of absence seizures as well as depressive-like behaviour were assessed by EEG recordings and the forced swimming test (FST).
In agreement with a previous report, both drugs continued to show antiepileptogenic effects 1 month after their discontinuation. Furthermore, ethosuximide improved depressive-like behaviour, whereas in contrast, levetiracetam worsened this symptom. However, none of the drugs maintained their antiepileptogenic effects 5 months after suspension, and in addition, animal behaviour in the FST returned to control conditions.
Overall, these results demonstrate that the antiepileptogenic effects of both ethosuximide and levetiracetam on absence seizure development and associated depressive-like behaviour in this model are only temporary.
WAG/Rij 大鼠是一种经过验证的遗传性癫痫发生、失神癫痫和抑郁共病的动物模型。一些治疗方法（例如乙琥胺）使用特定方案预防自发性失神发作的发展。因此，与丙戊酸相比，乙琥胺增加了儿童失神性癫痫发作的缓解率。考虑到在这种动物模型中，抗癫痫发生的效果在某些情况下不会随着时间的推移而保留，我们研究了乙琥胺和左乙拉西坦（在这种和其他动物癫痫模型中也具有抗癫痫发生作用）的抗癫痫发生效果是否会在停药 5 个月后保留。
年龄约为 1 个月的 WAG/Rij 大鼠长期接受两种药物中的一种治疗，剂量为约 80mg/kg/天，连续 17 周；停药后 1 个月和 5 个月，通过 EEG 记录和强迫游泳试验（FST）评估失神发作的发展以及抑郁样行为。
与之前的报告一致，两种药物在停药后 1 个月仍继续显示抗癫痫发生作用。此外，乙琥胺改善了抑郁样行为，而相反，左乙拉西坦则加重了这种症状。然而，两种药物均未在停药 5 个月后保留其抗癫痫发生作用，并且 FST 中的动物行为恢复到对照条件。
总的来说，这些结果表明，乙琥胺和左乙拉西坦对该模型中失神发作发展和相关抑郁样行为的抗癫痫发生作用只是暂时的。
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