Bac P, Pages N, Herrenknecht C, Dewulf C, Binet P, Durlach J
Laboratoire de Biologie Animale Appliquée, Faculté de Pharmacie, Châtenay Malabry, France.
Magnes Res. 1994 Jun;7(2):107-15.
The aim of our study was to analyse the possible implication of the serotoninergic system in the pathophysiology and the lethality of audiogenic seizures induced by magnesium deficiency, either by decreasing cerebral serotonin (5-HT) levels (p-chlorophenylalanine) or by increasing 5-HT levels in the brain (5-hydroxytryptophan, L-tryptophan, nialamide, fluoxetine). In magnesium-deficient mice, the percentages of audiogenic seizures and of fatal seizures were dependent on the time lapse between the p-chlorophenylalanine (PCPA) injection and the audiogenic test. The percentage was at least 24 h after the injection: in OF1 and C57BL/6 strains, PCPA fully protected the mice from seizure occurrence, whereas it only partially protected the animals of the other strains. 5-Hydroxytryptophan caused a decrease in the audiogenic seizures in magnesium-deficient OF1 mice as well as in control DBA/2 mice. In contrast L-tryptophan did not reduce the number of wild courses or of clonic and tonic seizures in either the magnesium-deficient OF1 strain or control DBA/2 mice. Nialamide and fluoxetine were only effective in decreasing the numbers of clonic and tonic convulsions of the audiogenic seizure without affecting the wild courses. The combination of nialamide and tryptophan caused a cessation of the audiogenic seizure phases in both magnesium-deficient OF1 and control DBA/2 mice. In contrast, the fluoxetine-tryptophan combination did not have the same effect on magnesium-deficient and non-magnesium-deficient mice. This work showed that the serotoninergic system plays a secondary role in the pathophysiology of audiogenic seizures in magnesium-deficient mice rather than in that of genetically audiosusceptible mice.
我们研究的目的是分析血清素能系统在镁缺乏诱发的听源性癫痫的病理生理学和致死性中可能产生的影响，方法是降低大脑血清素（5-羟色胺，5-HT）水平（对氯苯丙氨酸）或提高大脑中的5-HT水平（5-羟色氨酸、L-色氨酸、尼亚酰胺、氟西汀）。在缺镁小鼠中，听源性癫痫和致命性癫痫的发生率取决于注射对氯苯丙氨酸（PCPA）与听源性测试之间的时间间隔。该时间间隔至少为注射后24小时：在OF1和C57BL/6品系中，PCPA可完全保护小鼠不发生癫痫，而对其他品系的动物仅提供部分保护。5-羟色氨酸可使缺镁的OF1小鼠以及对照DBA/2小鼠的听源性癫痫发作减少。相比之下，L-色氨酸在缺镁的OF1品系或对照DBA/2小鼠中，均未减少狂奔发作或阵挛性和强直性癫痫发作的次数。尼亚酰胺和氟西汀仅在减少听源性癫痫的阵挛性和强直性惊厥次数方面有效，而不影响狂奔发作。尼亚酰胺和色氨酸的组合可使缺镁的OF1小鼠和对照DBA/2小鼠的听源性癫痫发作阶段停止。相比之下，氟西汀-色氨酸组合对缺镁和非缺镁小鼠没有相同的效果。这项研究表明，血清素能系统在缺镁小鼠听源性癫痫的病理生理学中起次要作用，而非在基因易患听源性癫痫的小鼠中起次要作用。
