Donepezil-induced improvement in delayed matching accuracy by young and old rhesus monkeys
Donepezil-induced improvement in delayed matching accuracy by young and old rhesus monkeys
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DOI：
10.1385/jmn:24:1:085
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发表时间：
2004-01-01
影响因子：
3.1
通讯作者：
Terry, AV
中科院分区：
文献类型：
--
作者：
Buccafusco, JJ;Terry, AV
多奈哌齐（Aricept（R））是一种长效胆碱酯酶抑制剂，广泛用于治疗阿尔茨海默病，以改善认知和记忆。认知增强剂类别中的许多药物，包括目前批准的药物和正在开发的药物，其临床适应症仅限于阿尔茨海默病。本研究的目的是确定多奈哌齐在改善猴子延迟匹配准确性方面的功效是否与年龄无关。在4个不连续的试验日期间，对9至29岁的雄性和雌性恒河猴（n = 17）施用多奈哌齐（10、25、50和100 μ g/kg，肌肉注射）。多奈哌齐治疗改善了平均任务准确性，但受试者间的变异性阻止了统计学意义。当单独考虑动物时，多奈哌齐的最有效剂量与组任务表现的高度显著增加相关，这与测试期间增强的回忆一致。与剂量-反应分析相关的变异性主要归因于受试者年龄，例如年龄较大的猴子需要更高剂量的多奈哌齐。然而，在对所有受试者有效的剂量下，年龄与任务准确性的改善之间没有关系。同样，基线任务熟练度和任务准确性的提高之间也没有联系。
Donepezil (Aricept(R)), a long-acting cholinesterase inhibitor, is widely used in the treatment of Alzheimer's disease to improve cognition and memory. Many drugs within the class of cognition-enhancing agents, both currently approved medications and those under development, have clinical indications narrowly relegated to Alzheimer's disease. The purpose of this study was to determine whether the efficacy attributed to donepezil in its ability to improve delayed matching accuracy by monkeys was independent of age. Male and female rhesus monkeys (n = 17) ranging from 9 to 29 yr of age were administered donepezil (10, 25,50, and 100 mug/kg, im) during 4 discrete test days. Donepezil treatment improved average task accuracy, but intersubject variability prohibited statistical significance. When animals were considered individually, the most effective dose of donepezil was associated with a highly significant increase in group task performance that was consistent with enhanced recall during testing. The variability associated with the dose-response analysis was attributable primarily to subject age, such that older monkeys required higher doses of donepezil. Yet at doses that were effective in all subjects, there was no relationship between age and the improvement in task accuracy. Likewise, there was no association between baseline task proficiency and improvement in task accuracy.