Intermittent Ethanol Access Increases Sensitivity to Social Defeat Stress.
Intermittent Ethanol Access Increases Sensitivity to Social Defeat Stress.
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间歇性获取乙醇会增加对社交失败压力的敏感性。
DOI：
10.1111/acer.14278
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Schank,JesseR
中科院分区：
文献类型：
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作者：
Nennig,SadieE;Fulenwider,HannahD;Eskew,JacobE;Whiting,KimberlyE;Cotton,MalloryR;McGinty,GabrielleE;Solomon,MatthewG;Schank,JesseR
背景酗酒与抑郁症的共病极为常见。最近的证据支持酒精暴露和压力敏感性之间的关系，这是抑郁症发展的一个潜在因素。我们的实验室最近表明，长期酒精灌胃增加了对社会失败压力（SDS）的敏感性。然而，自愿饮酒的影响，如间歇性乙醇访问（IEA）协议，失败的压力sensitivity.MethodsWe第一次评估了4周的IEA的影响，20%的酒精对阈下SDS暴露的敏感性。接下来，为了检查神经炎症机制，我们分析了IEA或慢性酒精暴露（通过胃内灌胃给予3.0 g/kg酒精10天）后NFkB抑制剂（IkB）的基因表达。然后，我们通过β-半乳糖苷酶免疫组织化学定量NF kB激活后IEA或慢性酒精灌胃NF kB-LacZ mice.ResultsIEA暴露小鼠显示增加敏感性阈下SDS相比，饮水对照。我们还发现，IEA后伏隔核（NAC）和杏仁核（AMY）中的IkB基因表达减少，但慢性酒精灌胃后没有改变。最后，我们观察到增加NFkB活性在中央杏仁核（CEA），基底外侧杏仁核（BLA），内侧杏仁核（MEA）IEA后，和增加NFkB活性仅在CEA慢性酒精gavage.ConclusionsThese研究结果进一步证实，以前的酒精暴露，在这种情况下间歇性自愿消费，可以影响抑郁样行为的发展，通过改变压力敏感性。此外，我们的研究结果表明，CEA作为酒精对应激敏感性的影响的潜在介质，因为在IEA和慢性酒精灌胃后，NF κ B在该区域被激活。因此，这项研究提供了关于NFkB通路改变的新见解，并确定了在未来评估NFkB在这些过程中的功能作用的实验中靶向的特定区域。
BackgroundComorbidity between alcoholism and depression is extremely common. Recent evidence supports a relationship between alcohol exposure and stress sensitivity, an underlying factor in the development of depression. Our laboratory has recently shown that chronic alcohol gavage increases sensitivity to social defeat stress (SDS). However, the effects of voluntary alcohol consumption, resulting from protocols such as intermittent ethanol access (IEA), on defeat stress sensitivity have yet to be elucidated.MethodsWe first assessed the effects of 4 weeks of IEA to 20% alcohol on sensitivity to subthreshold SDS exposure. Next, to examine neuroinflammatory mechanisms, we analyzed gene expression of inhibitor of NFkB (IkB) following IEA or chronic alcohol exposure (10 days of 3.0 g/kg alcohol via intragastric gavage). Then, we quantified NFkB activation via β‐galactosidase immunohistochemistry following IEA or chronic alcohol gavage in NFkB‐LacZ mice.ResultsIEA‐exposed mice displayed an increase in sensitivity to subthreshold SDS compared to water‐drinking controls. We also found that IkB gene expression was decreased in the nucleus accumbens (NAC) and amygdala (AMY) following IEA but was not altered following chronic alcohol gavage. Finally, we observed increased NFkB activity in the central amygdala (CEA), basolateral amygdala (BLA), and medial amygdala (MEA) after IEA, and increased NFkB activity solely in the CEA following chronic alcohol gavage.ConclusionsThese findings further corroborate that prior alcohol exposure, in this case intermittent voluntary consumption, can impact development of depressive‐like behavior by altering stress sensitivity. Furthermore, our results suggest the CEA as a potential mediator of alcohol's effects on stress sensitivity, as NFkB was activated in this region following both IEA and chronic alcohol gavage. Thus, this study provides novel insight on alterations in the NFkB pathway and identifies specific regions to target in future experiments assessing the functional role of NFkB in these processes.