Riekkinen M, Schmidt B, Kuitunen J, Riekkinen P
Department of Neuroscience and Neurology, University of Kuopio, Finland.
Eur J Pharmacol. 1997 Mar 12;322(1):1-9. doi: 10.1016/s0014-2999(96)00976-4.
The present experiment was designed to elucidate whether chronic dietary treatment with nimodipine (3 months, 1000 ppm) enhances water maze spatial navigation, passive avoidance behavior and locomotor activity, and whether such a treatment with nimodipine would interact with the therapeutic effect of acute metrifonate treatment. In young medial septum-lesioned rats, nimodipine had no effect by its own on cognitive or motor behavior, and did not enhance the water maze and passive avoidance behavior improving action of metrifonate (3 and 10 mg/kg. p.o.). Nimodipine treatment of aged rats did not markedly affect the deficit in motor performance. Single and combined nimodipine and metrifonate (3 and 10 mg/kg, p.o.) treatment of aged rats resulted in shorter escape distance values to the hidden water maze escape platform compared to those of control aged rats. The passive avoidance performance of aged rats was more effectively facilitated by a combined nimodipine and metrifonate treatment than by either of the drugs on their own. Following a washout period of 2.5 months the rats that were treated previously with nimodipine no longer performed better than aged controls in the water maze test. Furthermore, after the washout period metrifonate 10 mg/kg was no longer effective in improving the water maze behavior of the now 26-month-old rats irrespective of their chronic pretreatment. Taken together, these findings indicate that chronic nimodipine and acute metrifonate treatment may more effectively stimulate cognitive functioning than either of the treatments on their own.
本实验旨在阐明，用尼莫地平进行慢性饮食治疗（3个月，1000 ppm）是否能增强水迷宫空间导航能力、被动回避行为和运动活动，以及这种尼莫地平治疗是否会与急性美曲膦酯治疗的效果相互作用。在年轻的内侧隔区损伤大鼠中，尼莫地平自身对认知或运动行为没有影响，也没有增强美曲膦酯（3和10 mg/kg，口服）对水迷宫和被动回避行为的改善作用。尼莫地平治疗老年大鼠并未显著影响其运动能力缺陷。与对照老年大鼠相比，单次及联合使用尼莫地平和美曲膦酯（3和10 mg/kg，口服）治疗老年大鼠，使其在隐藏水迷宫逃避平台的逃避距离值更短。联合使用尼莫地平和美曲膦酯比单独使用任何一种药物更有效地促进了老年大鼠的被动回避行为表现。经过2.5个月的洗脱期后，先前用尼莫地平治疗的大鼠在水迷宫测试中的表现不再优于老年对照组。此外，洗脱期后，无论其慢性预处理情况如何，10 mg/kg的美曲膦酯对现在26个月大的大鼠的水迷宫行为改善不再有效。综上所述，这些发现表明，慢性尼莫地平和急性美曲膦酯治疗可能比单独使用任何一种治疗更有效地刺激认知功能。
