Department of Psychology, Binghamton University of the State University of New York, New York, USA.
Department of Psychology and Brain Research Center, University of British Columbia, Vancouver, British Columbia, Canada.
Neuroscience. 2019 Apr 15;404:153-164. doi: 10.1016/j.neuroscience.2019.01.062. Epub 2019 Feb 10.
Adolescent binge drinking renders young drinkers vulnerable to alcohol use disorders in adulthood; therefore, understanding alcohol-induced brain damage and associated cognitive dysfunctions is of paramount importance. Here we investigated the effects of binge-like adolescent intermittent ethanol (AIE) exposure on nonspatial working memory, behavioral flexibility and cholinergic alterations in the nucleus accumbens (NAc) in male and female rats. On postnatal days P25-57 rats were intubated with water or ethanol (at a dose of 5 g/kg) on a 2-day-on/2-day-off cycle and were then tested in adulthood on social recognition and probabilistic reversal learning tasks. During the social recognition task AIE-treated rats spent similar amounts of time interacting with familiar and novel juveniles, indicating an impaired ability to sustain memory of the familiar juvenile. During probabilistic reversal learning, AIE-treated male and female rats showed behavioral inflexibility as indicated by a higher number of trials needed to complete three reversals within a session, longer response latencies for lever selection, and for males, a higher number of errors as compared to water-treated rats. AIE exposure also reduced the number of cholinergic interneurons in the NAc in males and females. These findings indicate AIE-related pathologies of accumbal cholinergic interneurons and long lasting cognitive-behavioral deficits, which may be associated with cortico-striatal hypofunction.
青少年 binge drinking 使年轻饮酒者在成年后易患酒精使用障碍；因此，了解酒精引起的脑损伤和相关认知功能障碍至关重要。在这里，我们研究了 binge-like 青少年间歇性乙醇（AIE）暴露对雄性和雌性大鼠伏隔核（NAc）中非空间工作记忆、行为灵活性和胆碱能改变的影响。在出生后第 25-57 天，大鼠通过插管给予水或乙醇（剂量为 5g/kg），每两天一次，然后在成年期进行社交识别和概率反转学习任务测试。在社交识别任务中，AIE 处理的大鼠与熟悉和陌生的幼鼠互动的时间相同，表明它们维持对熟悉幼鼠记忆的能力受损。在概率反转学习中，AIE 处理的雄性和雌性大鼠表现出行为灵活性差，表现为完成三次反转所需的试验次数增加，选择杠杆的反应潜伏期延长，以及雄性大鼠的错误次数增加，与水治疗大鼠相比。AIE 暴露还减少了 NAc 中雄性和雌性的胆碱能中间神经元的数量。这些发现表明，AIE 相关的伏隔核胆碱能中间神经元的病理学和持久的认知行为缺陷，可能与皮质纹状体功能低下有关。
