Effects of Adolescent Alcohol Exposure on Learning and Hippocampal Function

青少年酒精暴露对学习和海马功能的影响

基本信息

批准号：
8706667
负责人：
H SCOTT SWARTZWELDER
金额：
$ 28.79万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2015-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8706667
关键词：
21 year old Acute Address Adolescence Adolescent Adult Affect Alcohol consumption Alcohols Animals Area Behavioral Brain Child Chronic Data Development Ethanol GABA Receptor Glutamate Metabolism Pathway Healthcare High Prevalence Hippocampal Formation Hippocampus (Brain)Human Impairment Interneurons Learning Long-Term Effects Long-Term Potentiation Measures Mediating Memory Motor Nerve Degeneration Neurons Neurophysiology - biologic function Pattern Proteins Proteomics Public Health Rattus Relative (related person)Reporting Sedation procedure Slice Synapses Synaptic Potentials Synaptic plasticity Whole-Cell Recordings Work Youth adolescent alcohol exposure alcohol effect alcohol exposure alcohol sensitivity aspartate receptor binge drinking critical period dentate gyrus design drinking memory process morris water maze motor impairment neocortical public health relevance receptor research study synaptic function underage drinking university student

项目摘要

DESCRIPTION (provided by applicant): Most people in the U.S. begin using alcohol during adolescence. Strikingly, 29% of 12th graders and 42% of college students report having had five or more drinks in a row during the last two weeks, and about 90% of the alcohol consumed by youth under the age of 21 in the U.S. is in the form of 'binge drinks.' This high prevalence of binge drinking occurs at a critical period for brain development that makes the adolescent brain uniquely vulnerable to negative consequences of alcohol exposure. We have consistently found that adolescent rats respond differently to acute ethanol than do adults. And studies in young humans report differential responsiveness to alcohol among children and late adolescents, relative to adults. Similar developmental differences in sensitivity to acute ethanol are found in electrophysiological studies as well in hippocampal and neocortical brain slices. In contrast, little is known about the long-term changes in behavioral or neural function that result from repeated alcohol exposure during adolescence, or about the cellular mechanisms that may underlie them. We have found that intermittent ethanol treatment during adolescence (AIE) blunts the normal maturational increase in sensitivity to ethanol-induced motor impairment in adulthood, and the normal maturational decrease in sensitivity to the acute effects of ethanol on learning. That is, AIE decreases adult sensitivity to the effects of ethanol on motor function, and increases adult sensitivity to ethanol induced learning impairments. We have now collected preliminary data indicating that AIE results in spatial learning impairments and diminished hippocampal long-term potentiation in adult rats. Thus our overall hypothesis is that AIE will alter adult hippocampal function, and learning and memory processes in adulthood. We have designed three sets of experiments to address this hypothesis. We will assess the effects of AIE on learning and memory as well as memory-related hippocampal functions at the circuit and cellular levels, during adulthood. The use of alcohol by adolescents represents a major public health concern with long-lasting impact on health care in the U.S. Recent studies have shown that alcohol affects brain function differently during adolescence than adulthood. However, the more pressing question relates to the possible long-term effects of repeated alcohol exposure during adolescence. The experiments proposed in this application will address this issue.

描述（由申请人提供）：大多数美国人在青春期开始饮酒。引人注目的是，29% 的 12 年级学生和 42% 大学生表示在过去两周内连续喝了五杯或更多酒，而美国 21 岁以下青少年消耗的酒精大约 90% 是在“狂饮”的形式。酗酒现象的高发发生在大脑发育的关键时期，这使得青少年的大脑特别容易受到酒精暴露的负面影响。我们一致发现，青春期大鼠对急性乙醇的反应与成年大鼠不同。对年轻人的研究表明，与成年人相比，儿童和青少年晚期对酒精的反应有所不同。在电生理学研究以及海马和新皮质脑切片中也发现了对急性乙醇敏感性的类似发育差异。相比之下，人们对青春期反复接触酒精所导致的行为或神经功能的长期变化，或者潜在的细胞机制知之甚少。我们发现，青春期间歇性乙醇治疗（AIE）会减弱成年期对乙醇引起的运动障碍的敏感性的正常成熟增加，以及对乙醇对学习的急性影响的敏感性的正常成熟降低。也就是说，AIE 降低了成人对乙醇对运动功能影响的敏感性，并增加了成人对乙醇引起的学习障碍的敏感性。我们现在收集的初步数据表明，AIE 会导致成年大鼠的空间学习障碍和海马长时程增强功能减弱。因此，我们的总体假设是 AIE 将改变成年海马功能以及成年期的学习和记忆过程。我们设计了三组实验来解决这个假设。我们将评估成年期间 AIE 对学习和记忆以及与记忆相关的海马功能在回路和细胞水平的影响。青少年饮酒是一个重大的公共卫生问题，对美国的医疗保健产生长期影响。最近的研究表明，酒精对青春期和成年期大脑功能的影响不同。然而，更紧迫的问题涉及青春期反复接触酒精可能产生的长期影响。本申请中提出的实验将解决这个问题。