Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure
Functional Alterations in the Dorsal Raphe Nucleus Following Acute and Chronic Ethanol Exposure
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DOI：
10.1038/npp.2014.205
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发表时间：
2015-02-01
影响因子：
7.6
通讯作者：
Kash, Thomas L.
中科院分区：
文献类型：
--
作者：
Lowery-Gionta, Emily G.;Marcinkiewcz, Catherine A.;Kash, Thomas L.
酗酒是一种普遍存在的疾病，其存在的部分原因是为了缓解负面情绪状态，例如戒酒期间经历的焦虑。新的证据表明，富含血清素的中缝背侧 (DR) 在乙醇戒断后的焦虑中发挥作用。目前的研究使用切片电生理学检查了雄性 DBA2/J 小鼠长期接触乙醇蒸气对 DR 的影响。我们发现，长期接触乙醇会导致社交方式缺陷，表明乙醇接触后 24 小时和 7 天焦虑样行为增加。在乙醇暴露后 24 小时，我们观察到 DR 中的兴奋性增加和自发抑制传递（抑制性突触后电流，IPSC）减少。在乙醇暴露后 7 天，我们观察到自发性和微型兴奋性传递（兴奋性突触后电流，EPSC）增加。由于急性乙醇会改变其他大脑区域的 GABA 传输，因此我们评估了乙醇暴露后 24 小时的 DR 中离体乙醇 (50 mM) 对微型 IPSC (mIPSC) 的影响。乙醇浴的应用增强了未接触乙醇和慢性间歇性乙醇暴露 (CIE) 小鼠细胞中 mIPSC 的振幅，但仅显着增强了 CIE 小鼠细胞中 mIPSC 的频率，表明 DR 神经元对 CIE 后急性乙醇的抑制作用更敏感。基于这些发现，我们假设慢性乙醇暴露后 DR 神经元的净兴奋有助于增强乙醇戒断期间的焦虑，并且 DR 神经元对随后乙醇暴露的敏感性增加可能介导急性乙醇缓解乙醇戒断期间焦虑的能力。
Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post-ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal.