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狂饮和高度饮酒——与静脉内酒精自我给药和潜在风险因素的关联。

Binge and high-intensity drinking-Associations with intravenous alcohol self-administration and underlying risk factors.

机构信息

Department of Psychiatry, Indiana University School of Medicine, Indianapolis, Indiana, USA.

Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.

出版信息

Addict Biol. 2022;27(6):e13228. doi: 10.1111/adb.13228.

DOI:10.1111/adb.13228
PMID:36301209
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9786574/
Abstract

Some styles of alcohol consumption are riskier than others. How the level and rate of alcohol exposure contribute to the increased risk of alcohol use disorder is unclear, but likely depends on the alcohol concentration time course. We hypothesized that the brain is sensitive to the alcohol concentration rate of change and that people at greater risk would self-administer faster. We developed a novel intravenous alcohol self-administration paradigm to allow participants direct and reproducible control over how quickly their breath alcohol concentration changes. We used drinking intensity and the density of biological family history of alcohol dependence as proxies for risk. Thirty-five alcohol drinking participants aged 21-28 years provided analytical data from a single, intravenous alcohol self-administration session using our computer-assisted alcohol infusion system rate control paradigm. A shorter time to reach 80 mg/dl was associated with increasing multiples of the binge drinking definition (p = 0.004), which was in turn related to higher density of family history of alcoholism (FHD, p = 0.04). Rate-dependent changes in subjective response (intoxication and stimulation) were also associated with FHD (each p = 0.001). Subsequently, given the limited sample size and FHD range, associations between multiples of the binge drinking definition and FHD were replicated and extended in analyses of the Collaborative Study on the Genetics of Alcoholism database. The rate control paradigm models binge and high-intensity drinking in the laboratory and provides a novel way to examine the relationship between the pharmacokinetics and pharmacodynamics of alcohol and potentially the risk for the development of alcohol use disorders.

摘要

一些饮酒方式比其他方式风险更大。酒精暴露的水平和速度如何增加酒精使用障碍的风险尚不清楚,但可能取决于酒精浓度的时程变化。我们假设大脑对酒精浓度变化率敏感,风险较高的人会自我给予更快的速度。我们开发了一种新的静脉内酒精自我给药范式,允许参与者直接且可重复地控制他们的呼吸酒精浓度变化的速度。我们使用饮酒强度和酒精依赖的生物学家族史密度作为风险的替代指标。35 名年龄在 21-28 岁之间的酒精饮用参与者使用我们的计算机辅助酒精输注系统速率控制范式,提供了单次静脉内酒精自我给药会议的分析数据。达到 80mg/dl 的时间越短,与增加 binge drinking 的倍数(p=0.004)相关,这反过来又与酒精依赖的家族史密度(FHD)更高相关(p=0.04)。主观反应(醉酒和兴奋)的速率依赖性变化也与 FHD 相关(均 p=0.001)。随后,鉴于样本量有限且 FHD 范围有限,在对酒精遗传学合作研究数据库的分析中,重复并扩展了 binge drinking 的倍数与 FHD 之间的关联。速率控制范式在实验室中模拟 binge 和高强度饮酒,并提供了一种新的方法来研究酒精的药代动力学和药效学与酒精使用障碍发展风险之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/58a56c579b0a/ADB-27-e13228-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/1f5de109ebac/ADB-27-e13228-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/5396d534b4bc/ADB-27-e13228-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/58a56c579b0a/ADB-27-e13228-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/1f5de109ebac/ADB-27-e13228-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/5396d534b4bc/ADB-27-e13228-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e51f/9786574/58a56c579b0a/ADB-27-e13228-g002.jpg

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