Chronic Intermittent Ethanol Exposure Selectively Increases Synaptic Excitability in the Ventral Domain of the Rat Hippocampus
Chronic Intermittent Ethanol Exposure Selectively Increases Synaptic Excitability in the Ventral Domain of the Rat Hippocampus
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DOI：
10.1016/j.neuroscience.2018.11.028
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发表时间：
2019-02-01
期刊：
影响因子：
3.3
通讯作者：
Weiner, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Ewin, Sarah E.;Morgan, James W.;Weiner, Jeffrey L.
许多研究表明海马失调与酒精使用障碍（AUD）的病理生理学有关。然而，在过去的二十年里，越来越多的证据揭示了海马背侧 (dHC) 和腹侧 (vHC) 海马亚区的不同功能作用，其中 dHC 主要参与空间学习和记忆，而 vHC 则调节焦虑和抑郁样行为。值得注意的是，据我们所知，还没有啮齿类动物研究检验长期乙醇暴露对沿背/腹轴突触传递的影响。为此，我们研究了 AUD 的慢性间歇性乙醇蒸气暴露 (CIE) 模型对 dHC 和 vHC 突触兴奋性的影响。成年雄性 Long-Evans 大鼠暴露于 CIE 或 AIR 10 天（12 小时/天；目标血液乙醇水平为 175-225 mg%），并在停药 24 小时后进行记录。正如预期的那样，该方案增加了高架十字迷宫和连续小巷测试中的焦虑样行为。细胞外记录显示 CA1 区域的突触兴奋与 CIE 相关显着增加，该区域仅局限于海马的腹侧区域。突触神经体部分的蛋白质印迹分析显示，CIE 后，调节突触强度的两种蛋白 GluA2 和 SK2 在 vHC 中表达失调，但在 dHC 中则不然。总之，这些发现表明腹侧 CA1 区域可能对长期乙醇暴露的适应不良效应特别敏感，并为一些可能导致戒断期间出现的负面情感状态的神经底物提供了新的见解。 (C) 2018 国际广播组织。由爱思唯尔有限公司出版。保留所有权利。
Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety- and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. To that end, we examined the effects of the chronic intermittent ethanol vapor exposure (CIE) model of AUD on dHC and vHC synaptic excitability. Adult male Long-Evans rats were exposed to CIE or AIR for 10 days (12 h/day; targeting blood ethanol levels of 175-225 mg%) and recordings were made 24 h into withdrawal. As expected, this protocol increased anxiety-like behaviors on the elevated plus-maze and successive alleys test. Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, were dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.