Behavioral Toxicity of Chronic Alcohol Drinking in Peri-Adolescent Monkeys

描述(由申请人提供)：青少年人群中娱乐场所过度饮酒仍然是一个严重且日益严重的公共卫生问题。调查报告称，10%的八年级学生和多达三分之一的高中生每周都会大量饮酒(5杯或更多)。在这个正规教育和大脑发育的关键时期大量饮酒可能会对后来的智力和认知功能构成严重风险。这项拟议的研究将使用非人类灵长类动物模型来评估青少年时期大量饮酒的后果，以及在一系列认知领域的任务获得和表现。该项目旨在确定因长期口服酒精摄入而受损的认知领域；冲动、酒精偏好和5-羟色胺转运体基因对行为变化的贡献；以及戒酒对青春期前猴子的认知和行为影响。这些研究遵循了一个探索性/发展性项目(R21AA013972，02/05/04-01/31/07)，其中确定了饮酒的雄性猴子在获得视觉-空间配对-联想学习任务和执行空间工作记忆的空间延迟反应任务方面受到损害。暴露在酒精中的动物在辨别学习和长期记忆测试中似乎没有受到损害，这表明这种影响可能对特定的认知领域具有选择性。拟议的研究将使用一种既定的程序，在试验组中产生持续的、高水平的酒精饮酒，这些实验组将被允许口服自我给药酒精(M-F)24个月。实验组和控制组的猴子将同时接受一系列全面的测试(部分源自人类的CATAB)，以探索学习、记忆、注意力和运动功能的多个方面。假设更多依赖额叶型执行功能的任务将优先受到长期饮酒的影响。据进一步预测，在长期戒除酒精后，可归因于酒精的认知差异将保持不变。与公共健康相关：酒精仍然是青少年中滥用最多的精神活性药物，多达一半的12年级学生报告在过去30天内消费。大多数12年级的饮酒者报告说，在前两周至少有一次重度饮酒事件(5杯或更多)。青春期是大脑发育的关键时期，也是获得和完善职业成功所必需的许多认知技能的关键时期。这些研究试图确定饮酒会干扰学习、记忆、注意力和其他关键认知功能的机制。

DESCRIPTION (provided by applicant): Recreational overuse of alcohol among adolescent populations remains a significant and growing public health concern. Surveys report that 10% of eighth graders and up to a third of high school seniors consume binge quantities (5 drinks or more) of alcohol on a weekly basis. Heavy drinking during this critical period of formal education and significant brain development may pose serious risk for later intellectual and cognitive function. The proposed studies will use a nonhuman primate model to evaluate the consequences of heavy drinking during adolescence task acquisition and performance in a range of cognitive domains. The project seeks to determine the cognitive domains which are impaired by chronic oral alcohol intake; contributions of impulsivity, alcohol preference and serotonin transporter genotype to behavioral change; and the cognitive and behavioral effects of withdrawal from chronic alcohol exposure in periadolescent monkeys. These studies follow an Exploratory/Developmental project (R21 AA013972, 02/05/04-01/31/07) in which it was established that male monkeys consuming alcohol are impaired in acquiring a visuo-spatial paired-associates learning task and in performing the spatial delayed-response task of spatial working memory. Alcohol-exposed animals appeared unimpaired on discrimination learning and long-term memory tests suggesting an effect which may be selective for specific cognitive domains. The proposed studies will use an established procedure to generate consistent, high levels of alcohol drinking in the experimental groups which will be allowed to orally self-administer alcohol (M-F) for 24 months. The experimental groups and control group monkeys will be concurrently trained on a comprehensive battery of tests (derived in part from the human CANTAB) which probe multiple aspects of learning, memory, attention and motor functions. It is hypothesized that tasks which depend more on frontal-type executive function will be preferentially affected by chronic alcohol drinking. It is further predicted that cognitive differences attributable to alcohol will be maintained upon long-term removal of access to alcohol. PUBLIC HEALTH RELEVANCE: Alcohol remains the most abused psychoactive drug in adolescents with up to half of 12th graders reporting consumption in the past 30 days. The majority of alcohol using 12th graders report at least one heavy drinking episode (5 drinks or more) in the prior two weeks. Adolescence is a critical time for both brain development and the acquisition and refinement of many cognitive skills necessary for vocational success. These studies seek to identify the mechanisms by which alcohol drinking can interfere with learning, memory, attention and other critical cognitive functions.