PROFOUND EFFECTS OF COMBINING CHOLINE AND PIRACETAM ON MEMORY ENHANCEMENT AND CHOLINERGIC FUNCTION IN AGED RATS
PROFOUND EFFECTS OF COMBINING CHOLINE AND PIRACETAM ON MEMORY ENHANCEMENT AND CHOLINERGIC FUNCTION IN AGED RATS
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DOI：
10.1016/0197-4580(81)90007-5
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发表时间：
1981-01-01
影响因子：
4.2
通讯作者：
BEER, B
中科院分区：
文献类型：
--
作者：
BARTUS, RT;DEAN, RL;BEER, B
为了深入了解减少[人类]与年龄相关的记忆障碍的可能方法，老年Fischer 344大鼠被给予赋形剂、胆碱、吡拉西坦或胆碱或吡拉西坦的组合。对每组动物进行1次被动回避任务的行为测试和生化测试，以确定海马区、皮质和纹状体胆碱和乙酰胆碱水平的变化。先前的研究表明，这种品系的大鼠在这种被动回避任务中存在严重的年龄相关缺陷，记忆障碍至少是部分原因。那些只给予胆碱(100 mg/kg)的受试者在行为任务上与给药的对照动物没有区别。服用吡拉西坦(100 mg/kg)的大鼠表现略好于对照组(P<；0.05)，但服用吡拉西坦/胆碱(各100 mg/kg)的大鼠的保持分数比单独服用吡拉西坦的大鼠高出数倍。单独服用两倍剂量的吡拉西坦(200 mg/kg)或胆碱(200 mg/kg)仍不能提高药物的保留率，与吡拉西坦和胆碱(各100 mg/kg)合用时一样。重复给药(1wk)的吡拉西坦/胆碱联合用药优于急性注射。胆碱和乙酰胆碱的区域测定显示，治疗和大脑区域之间存在有趣的差异。尽管给予胆碱可使纹状体和皮质的胆碱含量增加约50%，但乙酰胆碱水平的变化要微妙得多(仅为6%-10%)。在给予胆碱后，在海马区没有观察到明显的变化。单用吡拉西坦可显著增加海马区胆碱含量(88%)，并降低乙酰胆碱水平(19%)。服用吡拉西坦后，纹状体或皮质未见明显变化。胆碱和吡拉西坦的组合并不能增强单独使用这两种药物的效果，在某些情况下，联合用药的效果要明显得多。讨论了胆碱和吡拉西坦对胆碱能传递和其他神经功能的可能影响。讨论了这些效应如何减少老年受试者的特定记忆障碍。胆碱和吡拉西坦联合应用的效果与单独使用这两种药物的效果截然不同。为了在老年受试者中取得显著疗效，可能有必要减少大脑中多种相互作用的神经化学功能障碍，或者影响代谢途径缺陷的>；1参数的活性。
In an attempt to gain some insight into possible approaches to reducing age-related memory disturbances [in humans], aged Fischer 344 rats were administered either vehicle, choline, piracetam or a combination of choline or piracetam. Animals in each group were tested behaviorally for retention of a 1 trial passive avoidance task and biochemically to determine changes in choline and acetylcholine levels in hippocampus, cortex and striatum. Previous research has shown that rats of this strain suffer severe age-related deficits on this passive avoidance task and that memory disturbances are at least partially responsible. Those subjects given only choline (100 mg/kg) did not differ on the behavioral task from control animals administered vehicle. Rats given piracetam (100 mg/kg) performed slightly better than control rats (P < 0.05) but rats given the piracetam/choline combination (100 mg/kg of each) exhibited retention scores several times better than those given piracetam alone. Twice the dose of piracetam (200 mg/kg) or choline (200 mg/kg) alone still did not enhance retention nearly as well as when piracetam and choline (100 mg/kg of each) were administered together. Repeated administration (1 wk) of the piracetam/choline combination was superior to acute injections. Regional determinations of choline and acetylcholine revealed interesting differences between treatments and brain area. Although choline administration raised choline content about 50% in striatum and cortex, changes in acetylcholine levels were much more subtle (only 6-10%). No significant changes following choline administration were observed in the hippocampus. Piracetam alone markedly increased choline content in hippocampus (88%) and tended to decrease acetylcholine levels (19%). No measurable changes in striatum or cortex were observed following piracetam administration. The combination of choline and piracetam did not potentiate the effects seen with either drug alone and in certain cases the effects were much less pronounced under the drug combination. Possible effects of choline and piracetam on cholinergic transmission and other neuronal function were discussed. How these effects may reduce specific memory disturbances in aged subjects was discussed. The effects of combining choline and piracetam are quite different than those obtained with either drug alone. To achieve substantial efficacy in aged subjects it may be necessary to reduce multiple, interactive neurochemical dysfunctions in the brain or affect activity in > 1 parameter of a deficient metabolic pathway.