Decker M W, Gallagher M
Brain Res. 1987 Aug 4;417(1):59-69. doi: 10.1016/0006-8993(87)90179-x.
Administration of muscarinic cholinergic antagonists impairs performance on a variety of memory tasks. We examined the hypothesis that denervation of norepinephrine input to the forebrain would augment this effect of cholinergic antagonists. Administration of 6-hydroxydopamine into the dorsal noradrenergic bundle did not by itself alter the performance of rats on a radial maze working memory task. In Experiment 1, scopolamine, a muscarinic antagonist, impaired the performance of the NE-depleted animals more than that of animals in an operated control group. This result was again observed in Experiment 2; but here a lesion by order of dose administration interaction provided evidence for recovery from the effects of NE-depletion. In Experiment 3, it was found that NE denervation did not alter the functional status of basal forebrain cholinergic neurons as reflected in in vitro determination of sodium-dependent, high affinity choline uptake in hippocampus and cortex. These results suggest that an age-related decline in brain NE neurons, as well as further deterioration in this system in some cases of Alzheimer's disease, may contribute to the cognitive and memory deficits more typically ascribed to cholinergic dysfunction.
给予毒蕈碱胆碱能拮抗剂会损害多种记忆任务的表现。我们检验了这样一个假设：去甲肾上腺素输入前脑的神经支配被破坏会增强胆碱能拮抗剂的这种作用。向背侧去甲肾上腺素能束注射6-羟基多巴胺本身并不会改变大鼠在放射状迷宫工作记忆任务中的表现。在实验1中，毒蕈碱拮抗剂东莨菪碱对去甲肾上腺素耗竭的动物的表现损害比对手术对照组动物的损害更大。在实验2中再次观察到了这一结果；但在这里，按给药剂量顺序造成的损伤的相互作用为从去甲肾上腺素耗竭的影响中恢复提供了证据。在实验3中，发现去甲肾上腺素去神经支配并未改变基底前脑胆碱能神经元的功能状态，这一点在体外测定海马体和皮质中钠依赖性、高亲和力胆碱摄取时得到了反映。这些结果表明，大脑去甲肾上腺素能神经元与年龄相关的衰退，以及在某些阿尔茨海默病病例中该系统的进一步恶化，可能会导致通常归因于胆碱能功能障碍的认知和记忆缺陷。
