BACKGROUND Trauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic repeated predatory stress (CRPS) to query the extent to which sex interacts with CRPS to influence alcohol consumption, or cessation of consumption. METHODS Male (n = 16) and female (n = 15) C57BL/6 J mice underwent CRPS or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). Following the conclusion of two rounds of repeated stress, behavior was assessed in the open field. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) assessment (P90-131) with the options of 20 % ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess the drinking response to adulteration of the alcohol. RESULTS CRPS increased fecal corticosterone concentrations and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS reduced alcohol aversion in male mice such that higher concentrations of quinine were necessary to reduce alcohol intake as compared to control mice. CRPS did not alter alcohol-related behaviors in female mice. CONCLUSION Collectively, we demonstrate that repeated CRPS can induce anxiety-like behavior in both sexes but selectively influences the response to ethanol adulteration in males.

中文翻译：

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长期反复的掠食性应激诱导雄性小鼠对乙醇奎宁掺杂的抵抗力。

背景技术与创伤有关的精神病，例如创伤后应激障碍（PTSD）和饮酒障碍（AUD）是高度合并症，它们分别呈现出相反的性别特异性模式，女性中PTSD的患病率增加，而AUD诊断的患病率增加在男性中。同样，创伤后应激障碍是澳元发展的风险因素，关于性别对两种疾病共病发展的影响的数据相互矛盾。由于经历一次以上创伤事件的可能性很高，因此我们旨在利用慢性重复掠夺性应激（CRPS）来询问性别与CRPS相互作用以影响饮酒或戒酒的程度。方法雄性（n = 16）和雌性（n = 15）C57BL / 6 J小鼠在青春期（P35-P49）和成年期（P65-P79）两周接受CRPS或每日处理。在两轮反复的压力得出结论之后，在旷野评估行为。随后对小鼠进行两瓶选择的间歇性乙醇获取（IEA）评估（P90-131），并选择20％乙醇或水。建立饮酒行为后，将逐渐增加浓度的奎宁添加到乙醇中，以评估饮酒对掺假酒精的反应。结果与未暴露于CRPS的对照小鼠相比，CRPS增加了雄性和雌性小鼠在大视野中的粪便皮质类固醇浓度和焦虑样行为。与以前的报告一致，我们观察到酒精摄入量存在性别差异，因此女性每克体重所消耗的乙醇比男性多。此外，CRPS减少了雄性小鼠的酒精反感，因此与对照小鼠相比，较高的奎宁浓度对于减少酒精摄入是必需的。CRPS不会改变雌性小鼠的酒精相关行为。结论集体地，我们证明重复的CRPS可以在男女中诱发焦虑样行为，但是选择性地影响男性对乙醇掺假的反应。