Sex differences in binge alcohol drinking and the behavioral consequences of protracted abstinence in C57BL/6J mice.

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2023-11-13 DOI:10.1186/s13293-023-00565-0
Jean K Rivera-Irizarry, Lia J Zallar, Olivia B Levine, Mary Jane Skelly, Jared E Boyce, Thaddeus Barney, Ruth Kopyto, Kristen E Pleil
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Abstract

Background: Binge alcohol drinking is a risk factor linked to numerous disease states including alcohol use disorder (AUD). While men binge drink more alcohol than women, this demographic gap is quickly shrinking, and preclinical studies demonstrate that females consistently consume more alcohol than males. Further, women are at increased risk for the co-expression of AUD with neuropsychiatric diseases such as anxiety and mood disorders. However, little is understood about chronic voluntary alcohol drinking and its long-term effects on behavior. Here, we sought to characterize sex differences in chronic binge drinking and the effects of protracted alcohol abstinence on anxiety- and affective-related behaviors in males and females.

Methods: We assessed binge alcohol drinking patterns in male and female C57BL/6J mice using a modified Drinking in the Dark (DID) paradigm in which mice received home cage access to one bottle of 10% or 20% alcohol (EtOH) or water for 2 h per day on Days 1-3 and to two bottles (EtOH/H2O + H2O) for 24 h on Day 4 for 8 weekly cycles. Mice were then tested for the effects of protracted abstinence on avoidance, affective, and compulsive behaviors.

Results: Female mice consumed more alcohol than males consistently across cycles of DID and at 2, 4, and 24-h timepoints within the day, with a more robust sex difference for 20% than 10% EtOH. Females also consumed more water than males, an effect that emerged at the later time points; this water consumption bias diminished when alcohol was available. Further, while increased alcohol consumption was correlated with decreased water consumption in males, there was no relationship between these two measures in females. Alcohol preference was higher in 10% vs. 20% EtOH for both sexes. During protracted abstinence following chronic binge drinking, mice displayed decreased avoidance behavior (elevated plus maze, open field, novelty suppressed feeding) and increased compulsive behavior (marble burying) that was especially robust in females. There was no effect of alcohol history on stress coping and negative affective behaviors (sucrose preference, forced swim test, tail suspension) in either sex.

Conclusion: Female mice engaged in higher volume binge drinking than their male counterparts. Although females also consumed more water than males, their higher alcohol consumption was not driven by increased total fluid intake. Further, the effects of protracted abstinence following chronic binge drinking was driven by behavioral disinhibition that was more pronounced in females. Given the reciprocal relationship between risk-taking and alcohol use in neuropsychiatric disease states, these results have implications for sex-dependent alcohol drinking patterns and their long-term negative neuropsychiatric/physiological health outcomes in humans.

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C57BL/6J小鼠狂欢饮酒的性别差异和长期戒酒的行为后果
背景:酗酒是与包括酒精使用障碍(AUD)在内的许多疾病相关的危险因素。虽然男性酗酒比女性多,但这一人口差距正在迅速缩小,临床前研究表明,女性的饮酒量一直比男性多。此外,女性与神经精神疾病(如焦虑和情绪障碍)共同表达AUD的风险增加。然而,人们对长期自愿饮酒及其对行为的长期影响知之甚少。在这里,我们试图描述慢性酗酒的性别差异,以及长期戒酒对男性和女性焦虑和情感相关行为的影响。方法:我们使用改进的黑暗中饮酒(DID)范式评估了雄性和雌性C57BL/6J小鼠的狂饮模式,在第1-3天,小鼠在家里的笼子里每天喝一瓶10%或20%的酒精(EtOH)或水2小时,在第4天,喝两瓶(EtOH/H2O + H2O) 24小时,为期8周。然后对小鼠进行了长期禁欲对回避、情感和强迫行为的影响测试。结果:雌性小鼠在DID周期内以及一天中的2、4和24小时时间点比雄性小鼠消耗更多的酒精,在20%的EtOH比10%的EtOH时性别差异更明显。女性也比男性消耗更多的水,这一效应在较晚的时间点出现;当有酒精时,这种水消耗偏差就会减弱。此外,在男性中,饮酒增加与饮水减少相关,但在女性中,这两项指标之间没有关系。酒精偏好在10% EtOH高于20% EtOH的两性。在长期酗酒后的长期禁欲期间,小鼠表现出减少的回避行为(升高加上迷宫,开阔场地,抑制新奇的喂养)和增加的强迫行为(大理石埋葬),尤其是在雌性中。酒精史对应激应对和负性情感行为(蔗糖偏好、强迫游泳试验、悬尾)均无影响。结论:雌性小鼠比雄性小鼠更容易酗酒。虽然女性也比男性摄入更多的水,但她们更高的饮酒量并不是由总液体摄入量增加引起的。此外,长期酗酒后长期戒酒的影响是由行为去抑制驱动的,这在女性中更为明显。考虑到神经精神疾病状态下的冒险行为和饮酒之间的相互关系,这些结果对性别依赖的饮酒模式及其对人类神经精神/生理健康的长期负面影响具有启示意义。
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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
期刊最新文献
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