van Luijtelaar E L, Ates N, van der Staay F J
Department of Psychology, University of Nijmegen, The Netherlands.
Pharmacol Biochem Behav. 1994 Jul;48(3):575-9. doi: 10.1016/0091-3057(94)90316-6.
Although calcium antagonists possess antiepileptic properties in various models of epilepsy, their role after chronic administration and in models for generalized absence epilepsy has not been studied. Twenty-four male Wistar rats, aged 84-94 weeks, were chronically provided with EEG electrodes. Two groups received dietary nimodipine (860 ppm) for 14 and 21 weeks, respectively, while a control group received the same rat chow without nimodipine. The EEG was recorded for 3 h to establish the effects of nimodipine on spike-wave discharges. Next, 50 mg/kg pentylenetetrazol (PTZ) was injected to establish the effects on convulsive epilepsy, and the EEG was recorded for 30 min. All animals had spontaneous spike-wave discharges (SWD), but there were no differences between the three groups. However, chronic nimodipine treatment had a significant effect on PTZ-induced seizures: the group that had been treated with nimodipine for 21 weeks showed significantly more and longer-lasting seizures than the control group. The facilitating effects of chronically administered of nimodipine on PTZ-induced seizures are striking and opposite to those reported in the literature. In a second study, nimodipine was administered acutely, but no effects of nimodipine on PTZ-induced epilepsy could be detected. It can be concluded that chronic dietary administration of a calcium antagonist induces different effects on PTZ-induced seizures than acute administration in aged Wistar rats with spontaneous occurring SWD.
尽管钙拮抗剂在多种癫痫模型中具有抗癫痫特性，但它们在长期给药后的作用以及在全身性失神癫痫模型中的作用尚未得到研究。24只84 - 94周龄的雄性Wistar大鼠被长期植入脑电图电极。两组分别接受含尼莫地平（860 ppm）的饮食14周和21周，而对照组接受不含尼莫地平的相同大鼠饲料。记录脑电图3小时以确定尼莫地平对棘波放电的影响。接下来，注射50 mg/kg戊四氮（PTZ）以确定对惊厥性癫痫的影响，并记录脑电图30分钟。所有动物均有自发性棘波放电（SWD），但三组之间无差异。然而，尼莫地平长期治疗对PTZ诱导的癫痫发作有显著影响：接受尼莫地平治疗21周的组比对照组表现出明显更多且持续时间更长的癫痫发作。长期给予尼莫地平对PTZ诱导的癫痫发作的促进作用显著，且与文献报道的相反。在第二项研究中，急性给予尼莫地平，但未检测到尼莫地平对PTZ诱导的癫痫有任何影响。可以得出结论，在有自发性SWD的老年Wistar大鼠中，长期饮食给予钙拮抗剂与急性给予相比，对PTZ诱导的癫痫发作产生不同的影响。
