Alcohol exposure alters NMDAR function in the bed nucleus of the stria terminalis.

Alcohol exposure alters NMDAR function in the bed nucleus of the stria terminalis.
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DOI:
10.1038/npp.2009.69
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发表时间:
2009-10
期刊:
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
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长期接触酒精会导致剧烈的行为改变,包括焦虑样行为和抑郁的增加。这些改变被认为部分是由于调节情绪行为的大脑区域的适应,包括终纹床核(BNST),杏仁核的主要输出核。然而,迄今为止,还没有研究探讨体内酒精暴露对 BNST 突触功能的影响。为了更好地了解酒精如何改变神经元功能,我们使用从 C57Bl6 小鼠获得的脑切片中的全细胞电压钳记录和生物化学检查了体内酒精暴露改变 BNST 中谷氨酸能传递的能力。慢性间歇性而非连续性乙醇蒸气暴露增加了 NMDA 受体 (NMDAR) 介导的 EPSC 的时间总和。电生理学和生物化学方法都表明,这种差异不是由于谷氨酸释放的改变,而是由于含有 NR2B 的 NMDAR 水平的增加。此外,我们发现间歇性酒精暴露后,vBNST 中 NMDAR 的乙醇调节发生了改变。我们的结果支持这样的假设:NMDAR 介导的突触传递在扩展杏仁核的关键突触处变得敏感,因此可能是操纵与慢性酒精暴露急性戒断相关的行为缺陷的合适目标。
Chronic alcohol exposure can cause dramatic behavioral alterations, including increased anxiety-like behavior and depression. These alterations are proposed to be due in part to adaptations in the brain regions that regulate emotional behavior, including the bed nucleus of the stria terminalis (BNST), a principal output nucleus of the amygdala. However, to date there have been no studies that have examined the impact of in vivo alcohol exposure on synaptic function in the BNST. In order to better understand how alcohol can alter neuronal function, we examined the ability of in vivo alcohol exposure to alter glutamatergic transmission in the BNST using whole-cell voltage clamp recordings and biochemistry in brain slices obtained from C57Bl6 mice. Chronic intermittent, but not continuous, ethanol vapor exposure increased temporal summation of NMDA receptor (NMDAR) mediated EPSCs. Both electrophysiological and biochemical approaches suggest that this difference is not due to an alteration in glutamate release, but rather an increase in the levels of NR2B-containing NMDARs. Further, we found that ethanol modulation of NMDAR in the vBNST is altered following intermittent alcohol exposure. Our results support the hypothesis that NMDAR mediated synaptic transmission is sensitized at key synapses in the extended amygdala and thus may be a suitable target for manipulation of the behavioral deficits associated with acute withdrawal from chronic alcohol exposure.
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