Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems.
Sensitivity and Resilience to Predator Stress-Enhanced Ethanol Drinking Is Associated With Sex-Dependent Differences in Stress-Regulating Systems.
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DOI：
10.3389/fnbeh.2022.834880
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发表时间：
2022
影响因子：
3
通讯作者：
中科院分区：
文献类型：
--
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压力会增加酒精的饮用量，有证据证实创伤后应激障碍（PTSD）与酒精使用障碍（AUD）的发展之间存在关联。暴露于捕食者气味被认为是一种创伤性应激源，捕食者应激（PS）被广泛用作创伤后应激障碍的动物模型。我们之前的工作确定，反复暴露于间歇性PS显著增加naïve雄性和雌性C57BL/6J小鼠的焦虑相关行为、皮质酮水平和海马和前额皮质的神经元激活。在一个亚组动物中，间歇性暴露于PS也增加了随后的乙醇饮用，在合并PTSD和AUD的动物中，反应存在异质性。目前的研究建立在先前的工作基础上，并开始描述对ps增强饮酒的“敏感性”和“恢复力”。在基线、间歇性PS暴露和应激后测量乙醇饮用量；小鼠在禁欲24小时后被安乐死。中位数和四分位数范围的计算确定了“敏感”亚组（饮酒量比基线增加20%）和“弹性”亚组（与基线相比，饮酒量没有变化或减少）。在“敏感”亚组中，间歇性PS显著增加了24%的雄性（↑60%）和20%的雌性（↑71%）C57BL/6J小鼠随后的乙醇摄入量。血浆皮质酮水平在PS后显着增加，但在“敏感”亚组和“弹性”亚组中水平较低。在“敏感”和“弹性”亚组的代表性小鼠中，通过Western Blotting分析前额皮质和海马的促肾上腺皮质激素释放因子（CRF）受体1、CRF受体2、CRF结合蛋白和糖皮质激素受体的水平，与单独的naïve年龄匹配的小鼠进行比较。在前额叶皮层，CRF受体1、CRF受体2、CRF结合蛋白和糖皮质激素受体水平在“敏感”小鼠中明显高于naïve和“弹性”小鼠（仅在雌性中）。在海马区，无论性别，“弹性”小鼠与naïve和“敏感”小鼠相比，CRF受体1、CRF受体2和糖皮质激素受体水平均显著降低。这些结果表明，性别强烈影响酒精饮用和压力对调节压力和焦虑反应的蛋白质的影响。他们进一步建议，在AUD中靶向CRF系统和糖皮质激素受体需要考虑PTSD与AUD的合并症和治疗个体的性别。
Stress can increase ethanol drinking, and evidence confirms an association between post-traumatic stress disorder (PTSD) and the development of alcohol use disorder (AUD). Exposure to predator odor is considered a traumatic stressor, and predator stress (PS) has been used extensively as an animal model of PTSD. Our prior work determined that repeated exposure to intermittent PS significantly increased anxiety-related behavior, corticosterone levels, and neuronal activation in the hippocampus and prefrontal cortex in naïve male and female C57BL/6J mice. Intermittent PS exposure also increased subsequent ethanol drinking in a subgroup of animals, with heterogeneity of responses as seen with comorbid PTSD and AUD. The present studies built upon this prior work and began to characterize “sensitivity” and “resilience” to PS-enhanced drinking. Ethanol drinking was measured during baseline, intermittent PS exposure, and post-stress; mice were euthanized after 24-h abstinence. Calculation of median and interquartile ranges identified “sensitive” (>20% increase in drinking over baseline) and “resilient” (no change or decrease in drinking from baseline) subgroups. Intermittent PS significantly increased subsequent ethanol intake in 24% of male (↑60%) and in 20% of female (↑71%) C57BL/6J mice in the “sensitive” subgroup. Plasma corticosterone levels were increased significantly after PS in both sexes, but levels were lower in the “sensitive” vs. “resilient” subgroups. In representative mice from “sensitive” and “resilient” subgroups, prefrontal cortex and hippocampus were analyzed by Western Blotting for levels of corticotropin releasing factor (CRF) receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor, vs. separate naïve age-matched mice. In prefrontal cortex, CRF receptor 1, CRF receptor 2, CRF binding protein, and glucocorticoid receptor levels were significantly higher in “sensitive” vs. naïve and “resilient” mice only in females. In hippocampus, CRF receptor 1, CRF receptor 2 and glucocorticoid receptor levels were significantly lower in “resilient” vs. naïve and “sensitive” mice across both sexes. These results indicate that sex strongly influences the effects of ethanol drinking and stress on proteins regulating stress and anxiety responses. They further suggest that targeting the CRF system and glucocorticoid receptors in AUD needs to consider the comorbidity of PTSD with AUD and sex of treated individuals.
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与压力有关的精神疾病的性别差异：神经生物学观点。
影响因子：
7.4
作者：
Bangasser, Debra A.;Valentino, Rita J.
通讯作者：
Valentino, Rita J.
DOI：
10.1111/acer.12825
发表时间：
2015-09
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Albrechet-Souza L;Hwa LS;Han X;Zhang EY;DeBold JF;Miczek KA
通讯作者：
Miczek KA
影响因子：
4.7
作者：
Brancato A;Castelli V;Lavanco G;Tringali G;Micale V;Kuchar M;D'Amico C;Pizzolanti G;Feo S;Cannizzaro C
通讯作者：
Cannizzaro C
影响因子：
2.3
作者：
Finn, Deborah A.;Helms, Melinda L.;Devaud, Leslie L.
通讯作者：
Devaud, Leslie L.
影响因子：
8.2
作者：
Dielenberg, RA;McGregor, IS
通讯作者：
McGregor, IS