School of Psychology and Neuroscience, University of St Andrews, St Mary's College, South Street, St Andrews, Fife, Scotland KY16 9JP, UK.
Neuropharmacology. 2013 Oct;73:284-9. doi: 10.1016/j.neuropharm.2013.05.036. Epub 2013 Jun 14.
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.
研究表明，认知能力在大多数领域都会随年龄增长而下降，其中包括执行功能：特别是作为执行控制衡量标准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存在受损的情况。尽管胆碱能系统在与年龄相关的认知能力下降中起着重要作用，但关于胆碱能增强对注意力定势转移测试中与年龄相关的表现缺陷的影响的数据尚不存在。我们使用啮齿动物内/外注意力定势转移任务的 rodent version 在重复测量设计中，研究了胆碱酯酶抑制剂四氢吖啶-9-胺（tacrine）对老年大鼠（16-21 个月大）的反转学习和注意力定势转移的影响。辨别习得没有受损，但在测试之间，与年龄相关的反转学习缺陷仍然存在，并且 tacrine 的 3mg/kg 剂量可以改善这种缺陷。在定势转移方面没有与年龄相关的缺陷，但 tacrine 有降低定势转移成本的趋势。鉴于之前没有证据表明皮质乙酰胆碱在注意力定势转移任务中起作用，因此很可能是纹状体中改变的神经递质相互作用导致了这种改善。
