Thomas Elizabeth, Snyder Peter J, Pietrzak Robert H, Jackson Colleen E, Bednar Martin, Maruff Paul
Department of Psychology, University of Melbourne, Australia.
Neuropsychologia. 2008 Aug;46(10):2476-84. doi: 10.1016/j.neuropsychologia.2008.04.010. Epub 2008 Apr 22.
Scopolamine-induced deficits in cognitive and motor processes have been widely demonstrated in animals and humans, although the role of acetylcholine in working memory is not as well understood. This study examined the role of acetylcholine neurotransmission in visuospatial short term and working memory using the Groton Maze Learning Test (GMLT). The GMLT is a computerized hidden maze learning test that yields measures of component cognitive processes such as spatial memory, working memory, and visuomotor function, as well as their integration in trial-and-error problem solving. Healthy older adults were administered scopolamine (0.3 mg subcutaneous), the acetlycholinesterase inhibitor donepezil (5 mg oral), scopolamine with donepezil, or placebo. Compared to placebo, low-dose scopolamine led to performance deficits on all measures of the GMLT. The greatest scopolamine-induced deficits were observed in errors reflecting working memory processes (e.g., perseverative errors d=-2.98, and rule-break errors d=-2.49) and these impairments remained robust when statistical models accounted for scopolamine-related slowing in visuomotor speed. Co-administration of donepezil partially ameliorated scopolamine-related impairments and this effect was greatest for measures of working memory than short-term memory. By itself, donepezil was associated with a small improvement in visuomotor function. These results suggest that scopolamine disrupts processes required for rule maintenance and performance monitoring, in combination with visuomotor slowing and sequential location learning.
东莨菪碱引起的认知和运动过程缺陷在动物和人类中已得到广泛证实，尽管乙酰胆碱在工作记忆中的作用尚未得到充分理解。本研究使用格罗顿迷宫学习测试（GMLT），研究了乙酰胆碱神经传递在视觉空间短期记忆和工作记忆中的作用。GMLT是一种计算机化的隐藏迷宫学习测试，可得出空间记忆、工作记忆和视觉运动功能等认知过程组成部分的测量结果，以及它们在试错问题解决中的整合情况。健康的老年人被给予东莨菪碱（皮下注射0.3毫克）、乙酰胆碱酯酶抑制剂多奈哌齐（口服5毫克）、东莨菪碱与多奈哌齐的组合或安慰剂。与安慰剂相比，低剂量东莨菪碱导致GMLT所有测量指标的表现出现缺陷。在反映工作记忆过程的错误中观察到东莨菪碱引起的最大缺陷（例如，持续性错误d=-2.98，违反规则错误d=-2.49），当统计模型考虑到东莨菪碱相关的视觉运动速度减慢时，这些损伤仍然很明显。多奈哌齐与东莨菪碱联合使用可部分改善与东莨菪碱相关的损伤，这种效果在工作记忆测量指标上比短期记忆测量指标上更为明显。多奈哌齐单独使用时，与视觉运动功能的小幅改善有关。这些结果表明，东莨菪碱会破坏规则维持和表现监测所需的过程，同时伴有视觉运动减慢和顺序位置学习。
