Jäkälä P, Riekkinen M, Björklund M, Koivisto E, Schmidt B, Riekkinen P
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Eur J Pharmacol. 1996 Dec 30;318(2-3):239-50. doi: 10.1016/s0014-2999(96)00787-x.
The present study investigated if short-term treatment with an L-type Ca2+-channel inhibitor, nimodipine, can stimulate cognitive functioning and cortical electroencephalograph (EEG) arousal, and potentiate the effect of a cholinesterase inhibitor, metrifonate. Pretraining administration of nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on water maze and passive avoidance behavior of young neurologically intact controls, or water maze and passive avoidance performance failure induced by scopolamine pretreatment (i.p.; 0.4 mg/kg during the water maze and 2.0 mg/kg during the passive avoidance study), medial septal lesioning, or aging. Furthermore, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on the improvement by metrifonate (10 mg/kg, p.o.) of the water maze and passive avoidance failure induced by scopolamine pretreatment or medial septal lesioning, nor did it affect the potential of metrifonate (30 mg/kg. p.o.) to improve the water maze or passive avoidance behavior of aged rats. Finally, nimodipine (3, 10 and 30 mg/kg, p.o.) had no effect on spontaneously occurring thalamically generated neocortical high-voltage spindles or spectral EEG activity of young controls, nor did it alleviate the spectral EEG abnormality induced by scopolamine (0.2 mg/kg, i.p.) administration. Also, the combination of nimodipine 3 or 10 mg/kg and a subthreshold dose of metrifonate 10 mg/kg could not suppress high-voltage spindles or scopolamine treatment-induced spectral EEG activity abnormalities. According to the present results, short-term treatment with nimodipine does not stimulate cognitive functions or increase cortical EEG arousal, and does not block or potentiate the propensity of metrifonate to improve cognitive performance of rats.
本研究调查了L型钙通道抑制剂尼莫地平的短期治疗是否能刺激认知功能和皮层脑电图（EEG）觉醒，并增强胆碱酯酶抑制剂美曲膦酯的作用。在年轻的神经功能正常的对照组中，预训练给予尼莫地平（3、10和30mg/kg，口服）对水迷宫和被动回避行为没有影响，对东莨菪碱预处理（腹腔注射；水迷宫实验期间0.4mg/kg，被动回避实验期间2.0mg/kg）、内侧隔损伤或衰老诱导的水迷宫和被动回避行为失败也没有影响。此外，尼莫地平（3、10和30mg/kg，口服）对美曲膦酯（10mg/kg，口服）改善东莨菪碱预处理或内侧隔损伤诱导的水迷宫和被动回避行为失败没有影响，也不影响美曲膦酯（30mg/kg，口服）改善老年大鼠水迷宫或被动回避行为的潜力。最后，尼莫地平（3、10和30mg/kg，口服）对年轻对照组自发出现的丘脑产生的新皮层高压纺锤波或EEG频谱活动没有影响，也不能减轻东莨菪碱（0.2mg/kg，腹腔注射）给药诱导的EEG频谱异常。此外，尼莫地平3或10mg/kg与亚阈值剂量的美曲膦酯10mg/kg联合使用不能抑制高压纺锤波或东莨菪碱治疗诱导的EEG频谱活动异常。根据目前的结果，尼莫地平的短期治疗不能刺激认知功能或增加皮层EEG觉醒，也不能阻断或增强美曲膦酯改善大鼠认知表现的倾向。
