Schilling Markus, Wetzel Wolfram, Grecksch Gisela, Becker Axel
O.-v.-Guericke University Magdeburg, Faculty of Medicine, Institute of Pharmacology and Toxicology, Magdeburg, Germany.
Epilepsia. 2006 Dec;47(12):2075-82. doi: 10.1111/j.1528-1167.2006.00854.x.
The aim of the study was to define sleep disturbances in pentylenetetrazole (PTZ)-kindled rats and to explore the effects of the nootropic drug piracetam (Pir; 100 mg/kg) and the noncompetitive N-methyl-D-aspartate (NMDA)-antagonist MK-801 (0.3 mg/kg), which normalized learning performance in PTZ-kindled rats, on altered sleep parameters.
This is the first report showing a significant reduction in paradoxical sleep (PS) as a consequence of PTZ kindling. A correlation analysis revealed a significant correlation between seizure severity and PS deficit.
Pir did not interfere with seizure severity, and the substance did not ameliorate the PS deficit. However, the substance disconnected the correlation between seizure severity and PS deficit. MK-801, which reduced the severity of kindled seizures, counteracted the PS deficit efficaciously.
The results suggest that seizure severity and alterations in sleep architecture are two factors in the comprehensive network underlying learning impairments associated with epilepsy. Considering the results obtained in the experiments with Pir, reduction of seizure severity does not guarantee the reduction of impairments in the domain of learning.
本研究旨在明确戊四氮(PTZ)点燃大鼠的睡眠障碍,并探究益智药吡拉西坦(Pir;100mg/kg)和非竞争性N-甲基-D-天冬氨酸(NMDA)拮抗剂MK-801(0.3mg/kg)对PTZ点燃大鼠睡眠参数改变的影响,这两种药物可使PTZ点燃大鼠的学习能力恢复正常。
这是首份表明PTZ点燃导致异相睡眠(PS)显著减少的报告。相关性分析显示癫痫发作严重程度与PS缺乏之间存在显著相关性。
Pir不影响癫痫发作严重程度,且该药物不能改善PS缺乏。然而,该药物消除了癫痫发作严重程度与PS缺乏之间的相关性。MK-801可减轻点燃癫痫发作的严重程度,有效对抗PS缺乏。
结果表明,癫痫发作严重程度和睡眠结构改变是癫痫相关学习障碍综合网络中的两个因素。考虑到Pir实验获得的结果,癫痫发作严重程度的降低并不能保证学习领域损伤的减轻。