Hippocampal acetylcholine release during memory testing in rats: augmentation by glucose.
Hippocampal acetylcholine release during memory testing in rats: augmentation by glucose.
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DOI：
10.1073/pnas.93.10.4693
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发表时间：
1996-05
影响因子：
11.1
通讯作者：
M. Ragozzino;Katharine E. Unick;Katharine E. Unick;Paul E. Gold
中科院分区：
文献类型：
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作者：
M. Ragozzino;Katharine E. Unick;Katharine E. Unick;Paul E. Gold
几条证据表明，循环葡萄糖水平的适度增加可以增强记忆力。葡萄糖影响记忆的一个潜在机制可能是乙酰胆碱（ACh）释放的增加。本实验确定是否增强自发交替性能全身葡萄糖治疗海马乙酰胆碱输出的增加有关。使用HPLC-EC体内微透析，以12分钟的间隔评估细胞外ACh样品。腹腔注射生理盐水或葡萄糖（100、250或1000 mg/kg）后24分钟，在四臂十字迷宫中测试大鼠的自发交替行为并结合微透析收集。与生理盐水对照组的交替评分（44.7%）和ACh输出（58.9% vs基线）相比，250 mg/kg葡萄糖（而非100或1000 mg/kg）导致自发交替评分（69.5%）和ACh输出（121.5% vs基线）增加。葡萄糖诱导的交替评分和ACh输出的增加并不继发于自发活动的变化。生理盐水和葡萄糖（100-1000 mg/kg）处理对大鼠在保持室中海马ACh输出没有影响。这些发现表明，葡萄糖可能通过直接或间接增加ACh的释放来增强记忆。结果还表明，海马乙酰胆碱释放增加大鼠执行空间任务。此外，因为葡萄糖仅在行为测试期间增强ACh输出，所以循环葡萄糖可能仅在胆碱能细胞被激活的条件下调节ACh释放。
Several lines of evidence indicate that a modest increase in circulating glucose levels enhances memory. One mechanism underlying glucose effects on memory may be an increase in acetylcholine (ACh) release. The present experiment determined whether enhancement of spontaneous alternation performance by systemic glucose treatment is related to an increase in hippocampal ACh output. Samples of extracellular ACh were assessed at 12-min intervals using in vivo microdialysis with HPLC-EC. Twenty-four minutes after an intraperitoneal injection of saline or glucose (100, 250, or 1000 mg/kg), rats were tested in a four-arm cross maze for spontaneous alternation behavior combined with microdialysis collection. Glucose at 250 mg/kg, but not 100 or 1000 mg/kg, produced an increase in spontaneous alternation scores (69.5%) and ACh output (121.5% versus baseline) compared to alternation scores (44.7%) and ACh output (58.9% versus baseline) of saline controls. The glucose-induced increase in alternation scores and ACh output was not secondary to changes in locomotor activity. Saline and glucose (100-1000 mg/kg) treatment had no effect on hippocampal ACh output when rats remained in the holding chamber. These findings suggest that glucose may enhance memory by directly or indirectly increasing the release of ACh. The results also indicate that hippocampal ACh release is increased in rats performing a spatial task. Moreover, because glucose enhanced ACh output only during behavioral testing, circulating glucose may modulate ACh release only under conditions in which cholinergic cells are activated.