Tacrine improves reversal learning in older rats
Tacrine improves reversal learning in older rats
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DOI：
10.1016/j.neuropharm.2013.05.036
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发表时间：
2013-10-01
影响因子：
4.7
通讯作者：
Brown, Verity J.
中科院分区：
文献类型：
--
作者：
Tait, David S.;Chase, E. Alexander;Brown, Verity J.
据报道，包括执行功能在内的大多数认知领域都出现了与年龄相关的下降：特别是作为执行控制措施的注意力定势转移和反转学习，在人类和大鼠的老年人群中都受到了损害。尽管胆碱能系统在年龄相关性认知衰退中很重要，但在注意定势转移测试中，胆碱能增强对年龄相关表现缺陷的影响还没有数据可用。我们采用啮齿动物模型，采用重复测量设计，研究了胆碱酯酶抑制剂四氢吖啶-9-胺(他克林)对老年大鼠(16-21月龄)翻转学习和注意定势转移的影响。辨别习得没有受到损害，但在两次测试之间，与年龄相关的反转学习障碍持续存在，并通过3 mg/kg剂量的他克林改善。SET转换中没有发现与年龄相关的损害，但他克林有降低SET转换成本的趋势。鉴于之前缺乏皮质乙酰胆碱在注意定势转移任务中的作用的证据，纹状体中神经递质相互作用的改变很可能是这种改善的基础。(C)2013爱思唯尔有限公司。保留所有权利。
Age-related decline has been reported in most cognitive domains, including executive function: in particular, attentional set-shifting and reversal learning, as measures of executive control, are impaired in aged populations of both humans and rats. Despite the importance of the cholinergic system in age-related cognitive decline, no data are available on the effects of cholinergic enhancement on age-related performance deficits in tests of attentional set-shifting. We investigated the effects of the cholinesterase inhibitor tetrahydroacridin-9-amine (tacrine) on reversal learning and attentional set-shifting in older rats (aged 16-21 months) using the rodent version of the intradimensional/extradimensional attentional set-shifting task in a repeated-measures design. Discrimination acquisition was not impaired, but age-related impairments in reversal learning were persistent between tests, and ameliorated by the 3 mg/kg dose of tacrine. No age-related impairments in set-shifting were seen, but there was a tendency for tacrine to reduce the cost of shifting set. Given the lack of previous evidence for a role of cortical acetylcholine in attentional set-shifting tasks, it is likely that altered neurotransmitter interactions in striatum underlie this improvement. (C) 2013 Elsevier Ltd. All rights reserved.