Ferraro Giuseppe, Sardo Pierangelo
Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana G Pagano, Universitàd degli Studi di Palermo, Palermo, Italy.
Epilepsia. 2009 Apr;50(4):721-30. doi: 10.1111/j.1528-1167.2008.01956.x. Epub 2009 Feb 12.
We evaluated the possible additive effect induced by the administration of the anticonvulsant vigabatrin (VGB) and cholecystokinin-8 sulfate (CCK-8S) on an experimental model of partial complex seizures (maximal dentate gyrus activation, MDA). Moreover, the functional involvement of gamma-aminobutyric acid (GABA) neurotransmission was tested by iontophoretically administering bicuculline (GABA receptor antagonist) in the dentate gyrus.
Urethane anesthetized rats were pretreated with VGB (50, 100 or 200 mg/kg, i.p.) or CCK-8S (8 nmol/kg, i.p.) alone or coadministered with VGB (50 mg/kg, i.p.). Dentate gyrus epileptic activity was obtained through the repetitive electrical stimulation of the angular bundle. MDA latency, duration, and poststimulus afterdischarge (AD) duration were evaluated. The extracellular activity of some dentate neurons was recorded before and during bicuculline iontophoresis.
Only the higher dose of VGB reduced the mean duration of dentate MDA and AD. CCK-8S significantly decreased the number of animals exhibiting MDA responses, characterized by increased latency and shorter duration. The coadministration of CCK-8S and VGB (50 mg/kg) significantly increased the anticonvulsant effects, either reducing the number of responding animals or decreasing both MDA and AD durations. During bicuculline iontophoresis, all the modifications induced on the MDA-related activity of dentate neurons by the pretreatments (VGB and/or CCK-8S) were abolished.
The results indicate that CCK-8S significantly enhances the VGB-induced anticonvulsant effect in the MDA model of partial epilepsy, probably through an increase of GABA cerebral levels. Such increased anticonvulsant effect becomes evident by using VGB at a lower dose.
我们评估了抗惊厥药物氨己烯酸（VGB）和硫酸胆囊收缩素-8（CCK-8S）联合给药对部分性复杂癫痫发作实验模型（最大齿状回激活，MDA）可能产生的附加效应。此外，通过在齿状回中离子导入荷包牡丹碱（GABA受体拮抗剂）来测试γ-氨基丁酸（GABA）神经传递的功能参与情况。
用乌拉坦麻醉大鼠，分别单独给予VGB（50、100或200mg/kg，腹腔注射）或CCK-8S（8nmol/kg，腹腔注射），或VGB（50mg/kg，腹腔注射）与CCK-8S联合给药。通过对角束进行重复电刺激来诱发齿状回癫痫活动。评估MDA潜伏期、持续时间和刺激后放电（AD）持续时间。在荷包牡丹碱离子导入前和导入过程中记录一些齿状神经元的细胞外活动。
仅较高剂量的VGB降低了齿状回MDA和AD的平均持续时间。CCK-8S显著减少了出现MDA反应的动物数量，其特征为潜伏期延长和持续时间缩短。CCK-8S与VGB（50mg/kg）联合给药显著增强了抗惊厥作用，要么减少了有反应动物的数量，要么缩短了MDA和AD的持续时间。在荷包牡丹碱离子导入过程中，预处理（VGB和/或CCK-8S）对齿状神经元MDA相关活动所诱导的所有改变均被消除。
结果表明，CCK-8S可能通过提高大脑中GABA水平，在部分性癫痫的MDA模型中显著增强VGB诱导的抗惊厥作用。使用较低剂量的VGB时，这种增强的抗惊厥作用变得明显。
