{"title":"雄性Wistar大鼠青少年酗酒增加乙醇消耗量，降低成年早期的中毒敏感性，但不影响戒断。","authors":"Camila Ravasi, Agustín Salguero, Leonardo Marengo, Pedro Peñalver, Ricardo Marcos Pautassi","doi":"10.1080/00952990.2025.2464644","DOIUrl":null,"url":null,"abstract":"<p><p><i>Background:</i> Early adolescent ethanol exposure increases the risk of developing an alcohol use disorder. The mechanisms underlying this relationship may involve early ethanol exposure influencing anxiety or altering ethanol sensitivity.<i>Objectives:</i> To examine how adolescent binge drinking impacts sensitivity to ethanol intoxication, withdrawal symptoms, anxiety, compulsive behaviors, and ethanol intake in adulthood.<i>Methods:</i> Thirty-seven male Wistar rats self-administered ethanol during adolescence [postnatal days (PD) 27-45] or were housed under control conditions. In adulthood, the rats received intragastric intubations to simulate heavy alcohol (PDs 61-65, 3 daily doses of 0.0 or 1.5 g/kg) exposure. Intoxication and withdrawal symptoms were assessed (PDs 61-70), along with compulsive behaviors (marble burying test, PD68) and anxiety-related behaviors (light-dark box and elevated plus maze tests, PDs 69-70). Two-bottle choice tests provided measures of ethanol intake (PDs 75-87).<i>Results:</i> Adolescent binge exposure increased ethanol consumption in adulthood (<i>p</i> < .001; η2 = 0.51), with binge-exposed rats drinking 4.5-6.5 g/kg/day vs. 2 g/kg/day in controls. Binge-exposed rats exhibited reduced sensitivity to ethanol intoxication (<i>p</i> < .05; η2 = 0.17). Withdrawal symptoms were significantly greater (<i>p</i> < .005; η2 = 0.36) in rats exposed to alcohol during adulthood compared to controls, regardless of binge ethanol exposure. Anxiety or compulsive behaviors were unaffected by binge ethanol.<i>Conclusions:</i> Adolescent binge drinking led, in male rats, to significant increases in ethanol intake and reduced sensitivity to intoxication in adulthood. These findings suggest that early ethanol exposure results in decreased ethanol sensitivity, potentially increasing the likelihood of ethanol use. Adolescent binge drinking is a key vulnerability factor, and interventions should target this behavior.</p>","PeriodicalId":48957,"journal":{"name":"American Journal of Drug and Alcohol Abuse","volume":" ","pages":"1-12"},"PeriodicalIF":2.6000,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Adolescent binge drinking in male Wistar rats increases ethanol consumption and reduces intoxication sensitivity in early adulthood without affecting withdrawal.\",\"authors\":\"Camila Ravasi, Agustín Salguero, Leonardo Marengo, Pedro Peñalver, Ricardo Marcos Pautassi\",\"doi\":\"10.1080/00952990.2025.2464644\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><i>Background:</i> Early adolescent ethanol exposure increases the risk of developing an alcohol use disorder. The mechanisms underlying this relationship may involve early ethanol exposure influencing anxiety or altering ethanol sensitivity.<i>Objectives:</i> To examine how adolescent binge drinking impacts sensitivity to ethanol intoxication, withdrawal symptoms, anxiety, compulsive behaviors, and ethanol intake in adulthood.<i>Methods:</i> Thirty-seven male Wistar rats self-administered ethanol during adolescence [postnatal days (PD) 27-45] or were housed under control conditions. In adulthood, the rats received intragastric intubations to simulate heavy alcohol (PDs 61-65, 3 daily doses of 0.0 or 1.5 g/kg) exposure. Intoxication and withdrawal symptoms were assessed (PDs 61-70), along with compulsive behaviors (marble burying test, PD68) and anxiety-related behaviors (light-dark box and elevated plus maze tests, PDs 69-70). Two-bottle choice tests provided measures of ethanol intake (PDs 75-87).<i>Results:</i> Adolescent binge exposure increased ethanol consumption in adulthood (<i>p</i> < .001; η2 = 0.51), with binge-exposed rats drinking 4.5-6.5 g/kg/day vs. 2 g/kg/day in controls. Binge-exposed rats exhibited reduced sensitivity to ethanol intoxication (<i>p</i> < .05; η2 = 0.17). Withdrawal symptoms were significantly greater (<i>p</i> < .005; η2 = 0.36) in rats exposed to alcohol during adulthood compared to controls, regardless of binge ethanol exposure. Anxiety or compulsive behaviors were unaffected by binge ethanol.<i>Conclusions:</i> Adolescent binge drinking led, in male rats, to significant increases in ethanol intake and reduced sensitivity to intoxication in adulthood. These findings suggest that early ethanol exposure results in decreased ethanol sensitivity, potentially increasing the likelihood of ethanol use. Adolescent binge drinking is a key vulnerability factor, and interventions should target this behavior.</p>\",\"PeriodicalId\":48957,\"journal\":{\"name\":\"American Journal of Drug and Alcohol Abuse\",\"volume\":\" \",\"pages\":\"1-12\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-02-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"American Journal of Drug and Alcohol Abuse\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/00952990.2025.2464644\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"PSYCHOLOGY, CLINICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"American Journal of Drug and Alcohol Abuse","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/00952990.2025.2464644","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PSYCHOLOGY, CLINICAL","Score":null,"Total":0}
引用次数: 0
摘要
背景：青少年早期酒精暴露增加了发生酒精使用障碍的风险。这种关系的潜在机制可能涉及早期乙醇暴露影响焦虑或改变乙醇敏感性。目的：研究青少年酗酒对乙醇中毒的敏感性、戒断症状、焦虑、强迫行为和成年后乙醇摄入量的影响。方法：37只雄性Wistar大鼠在青春期[产后27-45天]自行给予乙醇或置于对照条件下。成年后，大鼠接受胃内插管，模拟重度酒精（pd值61-65，每天3次，剂量为0.0或1.5 g/kg）暴露。评估了中毒和戒断症状（pdds 61-70），以及强迫行为（大理石掩埋测试，PD68）和焦虑相关行为（光-暗盒和升高加迷宫测试，pdds 69-70）。两瓶选择测试提供了乙醇摄入量的测量（PDs 75-87）。结果：青少年酗酒会增加成年后的乙醇消耗量（p p p）结论：在雄性大鼠中，青少年酗酒会导致成年后乙醇摄入量显著增加，对中毒的敏感性降低。这些发现表明，早期乙醇暴露导致乙醇敏感性降低，潜在地增加了使用乙醇的可能性。青少年酗酒是一个关键的脆弱因素，干预措施应该针对这种行为。
Adolescent binge drinking in male Wistar rats increases ethanol consumption and reduces intoxication sensitivity in early adulthood without affecting withdrawal.
Background: Early adolescent ethanol exposure increases the risk of developing an alcohol use disorder. The mechanisms underlying this relationship may involve early ethanol exposure influencing anxiety or altering ethanol sensitivity.Objectives: To examine how adolescent binge drinking impacts sensitivity to ethanol intoxication, withdrawal symptoms, anxiety, compulsive behaviors, and ethanol intake in adulthood.Methods: Thirty-seven male Wistar rats self-administered ethanol during adolescence [postnatal days (PD) 27-45] or were housed under control conditions. In adulthood, the rats received intragastric intubations to simulate heavy alcohol (PDs 61-65, 3 daily doses of 0.0 or 1.5 g/kg) exposure. Intoxication and withdrawal symptoms were assessed (PDs 61-70), along with compulsive behaviors (marble burying test, PD68) and anxiety-related behaviors (light-dark box and elevated plus maze tests, PDs 69-70). Two-bottle choice tests provided measures of ethanol intake (PDs 75-87).Results: Adolescent binge exposure increased ethanol consumption in adulthood (p < .001; η2 = 0.51), with binge-exposed rats drinking 4.5-6.5 g/kg/day vs. 2 g/kg/day in controls. Binge-exposed rats exhibited reduced sensitivity to ethanol intoxication (p < .05; η2 = 0.17). Withdrawal symptoms were significantly greater (p < .005; η2 = 0.36) in rats exposed to alcohol during adulthood compared to controls, regardless of binge ethanol exposure. Anxiety or compulsive behaviors were unaffected by binge ethanol.Conclusions: Adolescent binge drinking led, in male rats, to significant increases in ethanol intake and reduced sensitivity to intoxication in adulthood. These findings suggest that early ethanol exposure results in decreased ethanol sensitivity, potentially increasing the likelihood of ethanol use. Adolescent binge drinking is a key vulnerability factor, and interventions should target this behavior.
期刊介绍：
The American Journal of Drug and Alcohol Abuse (AJDAA) is an international journal published six times per year and provides an important and stimulating venue for the exchange of ideas between the researchers working in diverse areas, including public policy, epidemiology, neurobiology, and the treatment of addictive disorders. AJDAA includes a wide range of translational research, covering preclinical and clinical aspects of the field. AJDAA covers these topics with focused data presentations and authoritative reviews of timely developments in our field. Manuscripts exploring addictions other than substance use disorders are encouraged. Reviews and Perspectives of emerging fields are given priority consideration.
Areas of particular interest include: public health policy; novel research methodologies; human and animal pharmacology; human translational studies, including neuroimaging; pharmacological and behavioral treatments; new modalities of care; molecular and family genetic studies; medicinal use of substances traditionally considered substances of abuse.
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