Ingram D K, Joseph J A, Spangler E L, Roberts D, Hengemihle J, Fanelli R J
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Neurobiol Aging. 1994 Jan-Feb;15(1):55-61. doi: 10.1016/0197-4580(94)90144-9.
Nimodipine is a calcium channel blocker reported to have beneficial effects on treatment of ischemic damage as well as the potential for retarding aspects of brain and behavioral aging when provided chronically to rats. We treated aged male F-344 rats (24 months) with nimodipine in SC pellets in the following doses: 0 (controls), 20 mg (low-dose), or 40 mg (high-dose) replenished after 6 weeks. After 3 months of treatment, surviving rats and a group of young controls (6 months) were tested in a behavioral battery involving exploratory activity in an open field and in a runwheel cage as well as motor abilities required for remaining on an inclined screen, suspended from a wire, and balanced on a rotorod. Rats were also pretrained for one-way active avoidance in a straight runway before being trained in a 14-unit T maze. During 20 trials rats were required to negotiate each of 5 maze segments within 10 s to avoid foot shock (0.8 mA). Nimodipine treatment produced no significant effects on body weight, food intake, or survival of aged rats. Analysis of behavioral results indicated significant age-related decline in performance of all tasks except in open-field behavior. Nimodipine treatment had no significant effects on behavioral performance of aged rats except in maze learning. Rats on the high-dose regimen performed significantly better than aged controls in the maze. The results indicate that chronic nimodipine treatment of aged rats had no toxic effects and might be beneficial for preventing age-related decline in learning performance.
尼莫地平是一种钙通道阻滞剂，据报道，它对缺血性损伤的治疗具有有益作用，并且长期给予大鼠时，具有延缓大脑和行为衰老方面的潜力。我们用尼莫地平的皮下植入丸剂以以下剂量治疗老年雄性F-344大鼠（24个月）：0（对照组）、20毫克（低剂量）或40毫克（高剂量），6周后补充。治疗3个月后，对存活的大鼠和一组年轻对照组（6个月）进行行为测试，测试内容包括在旷场和转轮笼中的探索活动，以及在倾斜屏幕上保持平衡、从电线上悬挂并在转棒上保持平衡所需的运动能力。在对大鼠进行14单元T迷宫训练之前，还在直跑道上对其进行了单向主动回避的预训练。在20次试验中，要求大鼠在10秒内通过5个迷宫片段中的每一个，以避免足部电击（0.8毫安）。尼莫地平治疗对老年大鼠的体重、食物摄入量或存活率没有显著影响。行为结果分析表明，除旷场行为外，所有任务的表现均与年龄相关地显著下降。尼莫地平治疗对老年大鼠的行为表现没有显著影响，除了在迷宫学习方面。高剂量方案组的大鼠在迷宫中的表现明显优于老年对照组。结果表明，长期用尼莫地平治疗老年大鼠没有毒性作用，可能有利于预防与年龄相关的学习能力下降。
