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

• 批准号: 8023025
• 负责人: H SCOTT SWARTZWELDER
• 金额: $ 30.67万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 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/8023025
• 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

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. PUBLIC HEALTH RELEVANCE: 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）：美国大多数人在青春期开始使用酒精。令人惊讶的是，在过去的两周中，有29％的12年级学生和42％的大学生报告连续五种或更多的饮料，而在美国21岁以下的青年饮酒中，约有90％的酒精为“暴饮暴食”。暴饮暴食的高流行率是在大脑发育的关键时期发生的，这使青少年大脑独特地容易受到酒精暴露的负面影响。我们一直发现，青少年对急性乙醇的反应与成年人不同。对年轻人的研究报告说，相对于成年人，儿童和晚期青少年的酒精反应差异。在电生理研究中发现了对急性乙醇的敏感性以及海马和新皮层脑切片中的类似发育差异。 相比之下，关于青春期反复暴露于酒精或可能是基础的细胞机制导致的行为或神经功能的长期变化知之甚少。我们发现，青春期（AIE）期间间歇性乙醇治疗在成年后对乙醇诱导的运动障碍的敏感性正常成熟，以及对乙醇对学习对乙醇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的影响的敏感性，并提高了成人对乙醇诱导的学习障碍的敏感性。 现在，我们收集了初步数据，表明AIE导致空间学习障碍并减少成年大鼠的海马长期增强。因此，我们的总体假设是AIE将改变成人海马功能，并在成年后的学习和记忆过程。我们设计了三组实验来解决这一假设。我们将在成年期评估AIE对在电路和细胞水平上与记忆相关的海马功能的影响。青少年对酒精的使用代表了美国的主要公共卫生问题，对美国的医疗保健产生了长期影响，最近的研究表明，在青春期，酒精对脑功能的影响与成年的影响不同。但是，更紧迫的问题与青春期重复酒精暴露的长期影响有关。本应用程序中提出的实验将解决此问题。 公共卫生相关性：青少年对酒精的使用代表了美国的主要公共卫生问题，对美国医疗保健的影响很大，最近的研究表明，在青春期，酒精对大脑的功能与成年的影响不同。但是，更紧迫的问题与青春期重复酒精暴露的长期影响有关。本应用程序中提出的实验将解决此问题。