Kowalska M, Disterhoft J F
Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, Illinois 60611.
Exp Neurol. 1994 May;127(1):159-66. doi: 10.1006/exnr.1994.1090.
Nimodipine, a 1,4-dihydropyridine calcium channel blocker, has been shown to enhance learning in aging rats, rabbits, and monkeys. Using an intravenous drug model, the relations among nimodipine dosage, nimodipine plasma concentration, and acquisition rate of the conditioned eyeblink response in aging rabbits were observed. Animals treated with nimodipine reached a behavioral criterion of 80% conditioned responses more quickly than did vehicle-treated control animals. Nimodipine doses produced marked behavioral effects, with statistically significant values starting at 0.5 micrograms/kg/min and reaching maximum efficacy at the minimal dose of 1 microgram/kg/min. Nimodipine at this dose exhibited an effect from the first day of infusion and facilitated learning rate threefold in comparison to control animals. Increasing the nimodipine dose to 3 and 5 micrograms/kg/min did not further facilitate learning rate. As nimodipine doses were augmented, the concentration of the nimodipine in plasma increased in a dose-related fashion. The most effective serum concentration for enhancing learning seemed to be distributed between 10 and 50 ng/ml. Concentrations above 50 ng/ml did not exert a more pronounced effect on the hippocampally dependent trace eyeblink conditioning task. The results of this study suggest that nimodipine may be useful in enhancing learning abilities in aging brain and have established the minimal serum concentration of nimodipine which must be achieved for this effect.
尼莫地平是一种1,4 - 二氢吡啶类钙通道阻滞剂，已被证明可增强老龄大鼠、兔子和猴子的学习能力。采用静脉给药模型，观察了老龄兔子中尼莫地平剂量、尼莫地平血浆浓度与条件性眨眼反应习得率之间的关系。接受尼莫地平治疗的动物比接受赋形剂治疗的对照动物更快达到80%条件反应的行为标准。尼莫地平剂量产生了显著的行为效应，统计学显著值从0.5微克/千克/分钟开始，在最低剂量1微克/千克/分钟时达到最大疗效。该剂量的尼莫地平从输注第一天就表现出效果，与对照动物相比，促进学习速度提高了三倍。将尼莫地平剂量增加到3和5微克/千克/分钟并没有进一步促进学习速度。随着尼莫地平剂量增加，血浆中尼莫地平浓度呈剂量相关方式增加。增强学习最有效的血清浓度似乎分布在10至50纳克/毫升之间。高于50纳克/毫升的浓度对海马依赖性痕迹眨眼条件反射任务没有更明显的影响。本研究结果表明，尼莫地平可能有助于增强老龄大脑的学习能力，并确定了产生这种效果所需达到的尼莫地平最低血清浓度。
