Penta Peter T, Villarreal Susanna, Rameas Caitlin I, Collins Ella C, Towner Trevor T, Varlinskaya Elena I, Werner David F
Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, USA.
Department of Psychology, Binghamton University, Binghamton, NY 13902-6000, USA.
Alcohol. 2025 Feb;122:71-80. doi: 10.1016/j.alcohol.2024.10.001. Epub 2024 Oct 21.
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.
乙醇戒断敏感性是酒精使用障碍发展的一个风险因素。青少年时期的大量饮酒往往包含反复的戒断期。实验室啮齿动物的青少年间歇性乙醇暴露会产生几种性别差异的神经生物学缺陷，但作为观察到的性别差异的一个促成因素，对戒断的敏感性尚不清楚。本研究评估了青春期单次和反复暴饮乙醇发作后的急性戒断以及反复暴饮发作后的长期戒断对雄性和雌性斯普拉格-道利大鼠社交焦虑样行为（通过社交探究显著减少来衡量）以及下丘脑（HYP）和中央杏仁核（CeA）中催产素（OXT）和加压素（AVP）系统基因表达的影响。雌性在单次暴饮发作后的戒断期间表现出社交焦虑样行为，而两性在反复暴饮发作后的急性戒断后均表现出社交焦虑样变化。经过一段时间的长期戒断后，只有雄性仍表现出与乙醇相关的社交改变。对单独的、未经社交测试的受试者的基因表达分析表明，青春期反复暴饮发作后的戒断增加了雄性HYP中的AVP基因表达，而降低了雌性中的AVP基因表达。雄性在反复暴饮发作后的急性戒断期间，CeA中的AVP和OXTR基因表达也增加，这些变化持续到成年期。总之，这些发现表明，青少年女性对急性和反复乙醇暴露后的戒断敏感，而男性对反复乙醇暴露后的戒断敏感，情感和转录变化持续到成年期。
