Kopf S R, Buchholzer M L, Hilgert M, Löffelholz K, Klein J
Department of Pharmacology, University of Mainz, Obere Zahlbacher Str. 67, D-55101, Mainz, Germany.
Neuroscience. 2001;103(2):365-71. doi: 10.1016/s0306-4522(01)00007-0.
The present study tests the effects of glucose and choline, the biosynthetic precursors of acetylcholine, on passive avoidance behaviour and hippocampal acetylcholine release measured by microdialysis in awake mice. Glucose (10 and 30mg/kg) or choline chloride (6-60mg/kg), given by i.p. injection immediately after training, dose-dependently enhanced retention in an inhibitory avoidance task. Combinations of low doses of glucose (10mg/kg) and choline chloride (20mg/kg) which alone were submaximally effective significantly increased retention latencies in a synergistic manner, an effect which was sensitive to atropine (0.5mg/kg). This beneficial effect vanished when higher doses of glucose or choline were combined. Basal hippocampal acetylcholine release in mice habituated to their environment was not affected by administration of glucose and choline. However, when hippocampal acetylcholine release was stimulated either by infusion of scopolamine (0.3microM) or by transferring the mice into a novel environment, the combination of glucose plus choline further increased acetylcholine release to a significant extent. We conclude that low doses of glucose and choline act synergistically to improve memory storage, an effect which is due to facilitation of acetylcholine release. This finding reinforces the view that central cholinergic functions are influenced under certain conditions by dietary intake of precursors.
本研究检测了乙酰胆碱的生物合成前体葡萄糖和胆碱对清醒小鼠被动回避行为以及通过微透析测定的海马乙酰胆碱释放的影响。训练后立即腹腔注射葡萄糖（10和30mg/kg）或氯化胆碱（6 - 60mg/kg），在抑制性回避任务中剂量依赖性地增强记忆保持。单独作用时效果次优的低剂量葡萄糖（10mg/kg）和氯化胆碱（20mg/kg）联合使用，以协同方式显著增加记忆保持潜伏期，该效应对阿托品（0.5mg/kg）敏感。当较高剂量的葡萄糖或胆碱联合使用时，这种有益效应消失。适应环境的小鼠海马基础乙酰胆碱释放不受葡萄糖和胆碱给药的影响。然而，当通过注入东莨菪碱（0.3μM）或通过将小鼠转移到新环境中刺激海马乙酰胆碱释放时，葡萄糖加胆碱的组合进一步显著增加乙酰胆碱释放。我们得出结论，低剂量的葡萄糖和胆碱协同作用以改善记忆存储，这一效应归因于乙酰胆碱释放的促进。这一发现强化了如下观点：在某些条件下，中枢胆碱能功能受前体饮食摄入的影响。
