Rüthrich H, Grecksch G, Krug M
Otto-von-Guericke University Magdeburg, Faculty of Medicine, Institute of Pharmacology and Toxicology, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1999 Oct;360(4):413-20. doi: 10.1007/s002109900086.
Kindling is a generally accepted model for studying epilepsy development in the context of overexpression of processes of neuronal plasticity. In previous studies we have shown that establishment of kindling by repeated application of subconvulsive doses of pentylenetetrazol (PTZ) also led to marked changes in hippocampal excitability and an impairment in learning behaviour. With the intention of further investigating the relationship between kindling development, kindling-induced changes in excitability and learning deficits, rats were chemically kindled under pretreatment with the nootropic drug piracetam. Furthermore, we tested acute piracetam effects on developed kindling seizures, the learning deficit and potentiation effects. At the investigated dose piracetam did not influence the kindling development. The kindling-induced potentiation of hippocampal field potentials was significantly diminished in piracetam-pretreated rats. Piracetam acutely injected completely antagonized this potentiation effect. Piracetam brought about a significant improvement in impaired learning performance in rats pretreated during kindling induction and acutely injected before the learning experiment, respectively. Possible correlations between the suppressing of the kindling related potentiation in hippocampal structures by piracetam and its beneficial effect on learning impairment are discussed as antagonizing overexpression of potentiation in the course of kindling.
点燃效应是在神经元可塑性过程过度表达的背景下研究癫痫发展的一种普遍接受的模型。在先前的研究中,我们已经表明,通过重复给予亚惊厥剂量的戊四氮(PTZ)来建立点燃效应,也会导致海马兴奋性的显著变化和学习行为的损害。为了进一步研究点燃效应的发展、点燃效应引起的兴奋性变化与学习缺陷之间的关系,在给予促智药吡拉西坦预处理的情况下,对大鼠进行化学点燃。此外,我们测试了吡拉西坦对已发展的点燃性癫痫发作、学习缺陷和增强效应的急性影响。在所研究的剂量下,吡拉西坦不影响点燃效应的发展。在吡拉西坦预处理的大鼠中,点燃效应引起的海马场电位增强显著减弱。急性注射吡拉西坦完全拮抗了这种增强效应。在点燃诱导期间进行预处理并在学习实验前急性注射的大鼠中,吡拉西坦分别使受损的学习表现得到了显著改善。作为对点燃过程中增强效应过度表达的拮抗作用,讨论了吡拉西坦对海马结构中与点燃相关的增强效应的抑制及其对学习障碍的有益作用之间可能存在的相关性。