Sex differences in binge-like EtOH drinking, corticotropin-releasing hormone and corticosterone: effects of β-endorphin.
Sex differences in binge-like EtOH drinking, corticotropin-releasing hormone and corticosterone: effects of β-endorphin.
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DOI：
10.1111/adb.12610
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发表时间：
2019-05
影响因子：
3.4
通讯作者：
Grisel JE
中科院分区：
文献类型：
--
作者：
Nentwig TB;Wilson DE;Rhinehart EM;Grisel JE
酗酒是一种越来越常见的危险饮酒模式，与许多健康问题（包括酒精使用障碍）相关。由于在有遗传风险的人群中，β-内啡肽 (β-E) 的基础血浆水平较低，并且 β-E 对酒精的反应明显增加，因此这种肽被认为会导致酗酒的易感性。动物模型表明，β-E 对消耗的影响可能具有性别依赖性。在这里，我们研究了具有不同水平 β-E 的转基因小鼠的暴食样 EtOH 消耗：具有 100% 肽的野生型对照 (β-E +/+)、经过组成性修饰以拥有 50% 野生型水平 (β-E +/-) 的杂合小鼠和完全缺乏合成 β-E 能力的小鼠 (−/−)。这三种基因型和两种性别均在 4 天、双瓶选择中进行评估，在黑暗模式中饮酒，限制使用 20% 乙醇。 β-E 缺乏决定了不同性别的饮酒模式，β-E -/- 雌性小鼠比野生型小鼠喝得更多，而雄性小鼠中未观察到这种效应。 β-E -/− 雌性小鼠还表现出基础焦虑升高、血浆皮质酮和扩展杏仁核中促肾上腺皮质激素释放激素 mRNA 升高，所有这些都通过自我给药 EtOH 恢复正常。这些数据表明，雌性小鼠过量摄入乙醇的风险增加与该药物改善过度活跃的焦虑/压力样状态的能力有关。综上所述，我们的研究强调了性别对乙醇消耗的神经肽调节的关键影响。
Binge drinking is an increasingly common pattern of risky use associated with numerous health problems, including alcohol use disorders. Because low basal plasma levels of β‐endorphin (β‐E) and an increased β‐E response to alcohol are evident in genetically at‐risk human populations, this peptide is thought to contribute to the susceptibility for disordered drinking. Animal models suggest that the effect of β‐E on consumption may be sex‐dependent. Here, we studied binge‐like EtOH consumption in transgenic mice possessing varying levels of β‐E: wild‐type controls with 100% of the peptide (β‐E +/+), heterozygous mice constitutively modified to possess 50% of wild‐type levels (β‐E +/−) and mice entirely lacking the capacity to synthesize β‐E (−/−). These three genotypes and both sexes were evaluated in a 4‐day, two‐bottle choice, drinking in the dark paradigm with limited access to 20% EtOH. β‐E deficiency determined sexually divergent patterns of drinking in that β‐E −/− female mice drank more than their wild‐type counterparts, an effect not observed in male mice. β‐E −/− female mice also displayed elevated basal anxiety, plasma corticosterone and corticotropin‐releasing hormone mRNA in the extended amygdala, and all of these were normalized by EtOH self‐administration. These data suggest that a heightened risk for excessive EtOH consumption in female mice is related to the drug's ability to ameliorate an overactive anxiety/stress‐like state. Taken together, our study highlights a critical impact of sex on neuropeptide regulation of EtOH consumption.
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影响因子：
3.4
作者：
Lehavot, Keren;Stappenbeck, Cynthia A.;Simpson, Tracy L.
通讯作者：
Simpson, Tracy L.
影响因子：
4.8
作者：
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通讯作者：
Hofmann SG
影响因子：
3
作者：
Barfield ET;Moser VA;Hand A;Grisel JE
通讯作者：
Grisel JE
影响因子：
3.4
作者：
Grisel, Judith E.;Bartels, Jessica L.;Allen, Stephani A.;Turgeon, Victoria L.
通讯作者：
Turgeon, Victoria L.
影响因子：
4.7
作者：
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通讯作者：
Roberto, Marisa