Sex-dependent effects of ethanol withdrawal from a single- and repeated binge episode exposures on social anxiety-like behavior and neuropeptide gene expression in adolescent rats

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol Pub Date : 2025-02-01 DOI:10.1016/j.alcohol.2024.10.001

Peter T. Penta, Susanna Villarreal, Caitlin I. Rameas, Ella C. Collins, Trevor T. Towner, Elena I. Varlinskaya, David F. Werner

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Abstract

Ethanol withdrawal sensitivity is a risk factor for the development of alcohol use disorder. Heavy episodic drinking during adolescence often encompasses repeated periods of withdrawal. Adolescent intermittent ethanol exposure of laboratory rodents produces several neurobiological deficits that differ between sexes, but the sensitivity to withdrawal as a contributor to the observed sex differences is not clear. The current study assessed the impact of acute withdrawal from a single- and repeated binge ethanol episodes during adolescence as well as protracted abstinence from repeated binge episodes on social anxiety-like behavior (indexed via significant decreases of social investigation) as well as oxytocin (OXT) and vasopressin (AVP) system gene expression in the hypothalamus (HYP) and central amygdala (CeA) in male and female Sprague Dawley rats. Females displayed social anxiety-like behavior during withdrawal from a single binge episode, whereas both sexes showed social anxiety-like changes following acute withdrawal from repeated binge episodes. After a period of protracted abstinence, only males still displayed ethanol-associated social alterations. Analysis of gene expression in separate, non-socially tested subjects revealed that withdrawal from repeated binge episodes during adolescence increased AVP gene expression in the HYP of males and decreased it in females. Males also displayed increased AVP and OXTR gene expression during acute withdrawal from repeated binge episodes in the CeA, with these changes persisting into adulthood. Together, these findings suggest that adolescent females are sensitive to withdrawal from both acute and repeated ethanol exposures, whereas males are sensitive to withdrawal from repeated ethanol exposures, with affective and transcriptional changes persisting into adulthood.

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单次和多次暴饮暴食暴露乙醇戒断对青春期大鼠社交焦虑样行为和神经肽基因表达的性别依赖性影响

乙醇戒断敏感性是导致酒精使用障碍的一个危险因素。青春期的大量偶发性饮酒往往包括反复的戒断期。实验室啮齿类动物在青春期间歇性接触乙醇会产生多种神经生物学缺陷，这些缺陷在性别上存在差异，但对戒断的敏感性是导致观察到的性别差异的一个因素，这一点尚不清楚。本研究评估了青春期单次和多次暴饮乙醇的急性戒断以及多次暴饮乙醇的长期戒断对雌雄 Sprague Dawley 大鼠社交焦虑样行为（以社交调查的显著减少为指标）以及下丘脑（HYP）和中央杏仁核（CeA）中催产素（OXT）和血管加压素（AVP）系统基因表达的影响。雌性大鼠在单次暴饮暴食后的戒断过程中表现出类似社交焦虑的行为，而雌雄大鼠在多次暴饮暴食后的急性戒断过程中都表现出类似社交焦虑的变化。在长期戒断后，只有雄性大鼠仍表现出与乙醇相关的社交变化。对单独的、非社交测试对象的基因表达分析表明，在青春期因反复酗酒而戒断后，男性 HYP 中的 AVP 基因表达增加，而女性则减少。在CeA中，男性在急性戒断重复酗酒发作时也显示出AVP和OXTR基因表达增加，这些变化一直持续到成年。这些研究结果表明，青春期女性对急性和反复暴露于乙醇的戒断敏感，而男性对反复暴露于乙醇的戒断敏感，其情感和转录变化会持续到成年。

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来源期刊

Alcohol 医学-毒理学

CiteScore

4.60

自引率

4.30%

发文量

审稿时长

15.6 weeks

期刊介绍： Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.