NIMODIPINE PRIOR TO ALCOHOL WITHDRAWAL PREVENTS MEMORY DEFICITS DURING THE ABSTINENCE PHASE
NIMODIPINE PRIOR TO ALCOHOL WITHDRAWAL PREVENTS MEMORY DEFICITS DURING THE ABSTINENCE PHASE
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DOI：
10.1016/j.neuroscience.2008.09.010
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发表时间：
2008-11-19
期刊：
影响因子：
3.3
通讯作者：
Little, H. J.
中科院分区：
文献类型：
--
作者：
Brooks, S. P.;Croft, A. P.;Little, H. J.
本文观察了L型钙通道阻滞剂二氢吡啶类药物尼莫地平对长期饮酒所致大鼠记忆力减退的影响。无论是单剂量的尼莫地平或2周的重复给药之前，从8个月的酒精消费撤出。通过物体识别测试和T迷宫测量记忆。两种尼莫地平治疗预防记忆缺陷时，这些都是在戒酒后1至2个月之间测量的。在记忆测试结束时，停止长期饮酒2个月后，大鼠大脑特定区域的糖皮质激素浓度增加，而血浆浓度没有变化。两种尼莫地平治疗方案都大大降低了脑糖皮质激素的升高。这些数据表明，在酒精戒断之前阻断L型钙通道可以防止长期饮酒引起的记忆缺陷。这表明，在急性戒断期给予特定的药物治疗，如尼莫地平，可以预防导致长期饮酒的后续不良反应的神经元变化。研究结果还表明，大脑局部糖皮质激素的增加可能与长期饮酒对记忆的不良影响有关。脑糖皮质激素水平的这种局部变化将对神经元功能产生重大影响。这些研究表明，L型钙通道和大脑糖皮质激素水平可能成为治疗酗酒者认知缺陷的新靶点。(C)2008年IBRO。由爱思唯尔有限公司出版。保留所有权利。
Effects of the dihydropyridine, nimodipine, an antagonist at L-type calcium channels, on the memory loss in rats caused by long term alcohol consumption were examined. Either a single dose of nimodipine or 2 weeks of repeated administration was given prior to withdrawal from 8 months of alcohol consumption. Memory was measured by the object recognition test and the T maze. Both nimodipine treatments prevented the memory deficits when these were measured between 1 and 2 months after alcohol withdrawal. At the end of the memory testing, 2 months after cessation of chronic alcohol consumption, glucocorticoid concentrations were increased in specific regions of rat brain without changes in plasma concentrations. Both nimodipine treatment schedules substantially reduced these rises in brain glucocorticoid. The data indicate that blockade of L-type calcium channels prior to alcohol withdrawal protects against the memory deficits caused by prolonged alcohol intake. This shows that specific drug treatments, such as nimodipine, given over the acute withdrawal phase, can prevented the neuronal changes responsible for subsequent adverse effects of long term consumption of alcohol. The results also suggest the possibility that regional brain glucocorticoid increases may be involved in the adverse effects of long term alcohol intake on memory. Such local changes in brain glucocorticoid levels would have major effects on neuronal function. The studies indicate that L-type calcium channels and brain glucocorticoid levels could form new targets for the treatment of cognitive deficits in alcoholics. (C) 2008 IBRO. Published by Elsevier Ltd. All rights reserved.