Flood J F
Geriatric Research, Education, and Clinical Center, Sepulveda, CA.
J Gerontol. 1988 Mar;43(2):B54-6. doi: 10.1093/geronj/43.2.b54.
The amnesias characteristic of Alzheimer's disease and other age-related dementias are refractory to conventional pharmacotherapy. A recent treatment strategy is to combine drugs, particularly cholinergic drugs, to improve their memory enhancing effect. We previously reported that in young, weakly trained mice, the combination of arecoline and tacrine was more effective on a mg/kg basis than either drug administered alone. This was true whether the route of administration was intracerebroventricular, subcutaneous, or oral. These drug treatments have also been found to improve retention in 24-month-old mice. Mice 24 months of age show very poor recall one week after training. Failing memory must develop over time but may only be detected in mice younger than 24 months of age when the retention test interval is substantially longer. We now report that 18-month-old mice trained to avoid footshock in a T-maze show poor retention when tested two months after training and drug administration. Subcutaneous administration of arecoline, tacrine, and arecoline plus tacrine all enhanced retention of 18-month-old mice compared to the saline-injected control. The combination was as effective as the single drug treatments even though 96% less arecoline and 99.7% less tacrine were administered.
阿尔茨海默病及其他与年龄相关的痴呆症所特有的失忆症对传统药物治疗无效。最近的一种治疗策略是联合用药，尤其是胆碱能药物，以提高其增强记忆的效果。我们之前报道过，在年轻、训练不足的小鼠中，按毫克/千克计算，槟榔碱和他克林联合使用比单独使用任何一种药物都更有效。无论给药途径是脑室内、皮下还是口服，都是如此。这些药物治疗也被发现能改善24月龄小鼠的记忆保持能力。24月龄的小鼠在训练一周后记忆表现非常差。记忆衰退肯定是随着时间发展的，但可能只有在24月龄以下的小鼠中才能检测到，此时记忆保持测试的间隔时间要长得多。我们现在报告，在T迷宫中接受避免电击训练的18月龄小鼠，在训练和给药两个月后进行测试时，记忆保持能力较差。与注射生理盐水的对照组相比，皮下注射槟榔碱、他克林以及槟榔碱加他克林均增强了18月龄小鼠的记忆保持能力。联合用药与单一药物治疗效果相当，尽管槟榔碱的用量减少了96%，他克林的用量减少了99.7%。
