Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression.
Bidirectional relationship between alcohol intake and sensitivity to social defeat: association with Tacr1 and Avp expression.
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DOI：
10.1111/adb.12494
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发表时间：
2018-01
影响因子：
3.4
通讯作者：
Schank JR
中科院分区：
文献类型：
--
作者：
Nelson BS;Sequeira MK;Schank JR
虽然流行病学研究表明，酗酒通常与情感障碍共存，但这种关联的因果方向尚不清楚。我们使用小鼠模型研究了这种关系，包括社交失败压力（SDS）、社交互动（SI）和自愿饮酒。暴露于 SDS 的 C57BL6/J 小鼠分为两个亚群，表达抑郁样表型的亚群（“易感”）和不表达抑郁样表型的亚群（“有弹性”）。首先，我们对暴露于 SDS 的小鼠进行分层并测量它们的自愿饮酒量。接下来，我们确定未接触过酒精的小鼠的 SI 行为是否可以预测酒精摄入量。最后，我们评估了暴饮暴食对 SDS 敏感性的影响。我们对与抑郁、成瘾和社会行为有关的大脑区域中的 Tacr1（神经激肽-1 受体基因）和 Avp（加压素肽基因）mRNA 进行了定量。我们发现，与弹性小鼠相比，易感小鼠消耗了更多的酒精，这表明抑郁样表型与酒精摄入量增加有关。有趣的是，我们观察到在应激小鼠和未曾饮酒的小鼠中，SI 与酒精摄入量呈负相关，这表明 SI 的个体差异与酒精偏好相关。最后，酒精预处理增加了对 SDS 的敏感性，表明酒精暴露改变了对社会压力的敏感性。 mRNA 定量显示，Tacr1 和 Avp 表达增加通常与 SI 降低和酒精摄入量增加相关。 C57BL6/J小鼠是近交系；因此，行为和基因表达的个体差异很可能是由表观遗传因素驱动的。总的来说，这些结果支持酒精暴露和对压力的敏感性之间存在双向关系，而压力易感性与神经肽表达的变化有关。
While epidemiological studies show that alcohol abuse is often comorbid with affective disorders, the causal direction of this association is unclear. We examined this relationship using mouse models including social defeat stress (SDS), social interaction (SI), and voluntary alcohol consumption. C57BL6/J mice exposed to SDS segregate into two subpopulations, those that express depressive-like phenotypes (“susceptible”), and those that do not (“resilient”). First, we stratified SDS-exposed mice and measured their voluntary alcohol consumption. Next, we determined if SI behavior in alcohol-naïve mice could predict alcohol intake. Finally, we assessed the effect of binge-like alcohol exposure on sensitivity to SDS. We quantified Tacr1 (neurokinin-1 receptor gene) and Avp (vasopressin peptide gene) mRNA in brain regions involved in depression, addiction, and social behavior. We found that susceptible mice consumed more alcohol compared to resilient mice suggesting that depression-like phenotypes associate with increased alcohol intake. Interestingly, we observed a negative correlation between SI and alcohol intake in stress- and alcohol-naïve mice, suggesting that individual differences in SI associate with alcohol preference. Finally, alcohol pretreatment increased sensitivity to SDS, indicating that alcohol exposure alters sensitivity to social stress. Quantification of mRNA revealed that increased expression of Tacr1 and Avp generally associated with decreased SI and increased alcohol intake. C57BL6/J mice are an inbred strain; thus it is likely that individual differences in behavior and gene expression are driven by epigenetic factors. Collectively, these results support a bidirectional relationship between alcohol exposure and susceptibility to stress that is associated with variations in neuropeptide expression.
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DOI：
10.1126/science.1249240
发表时间：
2014-04-18
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Friedman AK;Walsh JJ;Juarez B;Ku SM;Chaudhury D;Wang J;Li X;Dietz DM;Pan N;Vialou VF;Neve RL;Yue Z;Han MH
通讯作者：
Han MH
影响因子：
3.3
作者：
Funk, D;Li, Z;Lê, AD
通讯作者：
Lê, AD
影响因子：
3.4
作者：
Hansson, Anita C.;Cippitelli, Andrea;Heilig, Markus
通讯作者：
Heilig, Markus
影响因子：
7.6
作者：
Covington, HE;Kikusui, T;Miczek, KA
通讯作者：
Miczek, KA
影响因子：
3.4
作者：
Funk, D;Harding, S;Lê, AD
通讯作者：
Lê, AD