Neonatal Ethanol-Induced Memory Impairments in Rats

新生大鼠乙醇引起的记忆障碍

• 批准号: 7227123
• 负责人: PAMELA S HUNT
• 金额: $ 10.17万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227123
• 关键词: Acute; Address; Affect; Alcohol-Related Disorders; Alcohol-Related Neurodevelopmental Disorder; Alcohols; Animal Experiments; Animal Model; Animals; Applications Grants; Behavior; Behavioral; Biological Assay; Biological Models; Brain region; Child; Choline; Cholinergic Agents; Cholinesterase Inhibitors; Chronic; Cognitive; Cognitive deficits; Complex; Condition; Data; Diagnosis; Diet; Disruption; Dose; Ethanol; Exhibits; Extinction (Psychology); Fetal Alcohol Syndrome; Fright; Goals; Heart Rate; Hippocampus (Brain); Human; Impairment; Individual; Investigation; Knowledge; Learning; Literature; Measures; Memory; Memory impairment; Methodology; Modeling; Neonatal; Neonatal Alcohol Exposure; Outcome; Pharmacological Treatment; Positioning Attribute; Prevention; Procedures; Process; Psychological Transfer; Rattus; Recruitment Activity; Reporting; Research; Research Personnel; Research Proposals; Reversal Learning; Rodent Model; Role; Structure; Supplementation; System; Third Pregnancy Trimester; Training Technics; Variant; Work; alcohol effect; alcohol exposure; base; cholinergic; classical conditioning; conditioned fear; conditioning; day; executive function; exposed human population; falls; frontal lobe; memory process; memory recognition; programs; research study; response; way finding

DESCRIPTION (provided by applicant): The overall goal of this research is to expand the investigation of alcohol-induced memory impairments in a rodent model of Alcohol-Related Neurodevelopmental Disorder (ARND). Individuals diagnosed with Fetal Alcohol Syndrome (FAS) or ARND exhibit significant deficits in a variety of memory domains, including explicit, declarative, associative, extinction, and spatial. To date, the study of memory impairments using animal models has focused almost exclusively on tasks that require spatial learning and spatial navigation. The experiments outlined in this research proposal are intended to expand the study of memory deficits by using tasks that have no overt spatial component. We intend to address four specific aims in this research. In all experiments, animals will be administered alcohol during the neonatal period (days 4-9) to model third trimester human exposure. The first aim is intended to further explore short- and long-term nonassociative memory deficits by expanding upon our previous work using habituation of the heart rate orienting response. These experiments will address issues of dose-response functions, limited durations of alcohol exposure, and variations in methodology to promote nonassociative learning. The second aim will examine the relation between nonassociative and associative learning using a Pavlovian fear conditioning procedure and measuring several fear-related conditioned responses (behavior, heart rate, and fear-potentiated startle). The third aim will expand the study of declarative and explicit memory impairments by investigating alcohol-induced changes in trace conditioning and contextual conditioning. In addition, extinction of the conditioned responses acquired in these associative tasks will be evaluated to increase our understanding of alcohol effects on one type of executive function. Finally, the experiments addressing the last aim are geared toward an initial examination of potential behavioral and pharmacological treatments to ameliorate memory impairments resulting from alcohol exposure. The behavioral training techniques are based on transfer of learning from one situation to another, while the pharmacological treatments will include acute administration of cholinesterase inhibitors or chronic choline supplementation to the diet of the offspring. Collectively, these studies will further our understanding of memory impairments observed in humans with FAS or ARND by using tasks with an animal model that fall outside the realm of explicit spatial learning and memory. The potential for amelioration of these cognitive deficits using both behavioral and pharmacological strategies will provide important information regarding treatment approaches for afflicted individuals.

描述（由申请人提供）：这项研究的总体目标是扩大对酒精相关神经发育障碍（ARND）啮齿动物模型中对酒精诱导的记忆障碍的研究。诊断为胎儿酒精综合征（FAS）或ARND的个体在各种记忆域中表现出明显的缺陷，包括显式，声明性，联想，灭绝和空间。迄今为止，使用动物模型对记忆障碍的研究几乎完全集中在需要空间学习和空间导航的任务上。该研究建议中概述的实验旨在通过使用没有明显空间成分的任务来扩大记忆缺陷的研究。我们打算解决这项研究的四个具体目标。在所有实验中，在新生儿期（第4-9天）中，将向动物进行酒精，以模拟三个月的人类暴露。第一个目标旨在通过使用习惯性心率定向反应来扩展我们以前的工作，以进一步探索短期和长期的非社交记忆缺陷。这些实验将解决剂量反应功能，酒精暴露持续时间有限以及促进非社交学习的方法的差异。第二个目的将使用帕夫洛维亚恐惧调节程序来检查非缔合性学习和联想学习之间的关系，并测量几种与恐惧有关的条件反应（行为，心率和恐惧感激发的惊吓）。第三个目标将通过研究酒精引起的痕量调理和上下文调节的变化来扩大声明性和明确记忆障碍的研究。此外，将评估在这些关联任务中获得的条件响应的灭绝，以提高我们对酒精对一种执行功能的影响的理解。最后，针对最后一个目标的实验旨在初步检查潜在的行为和药理治疗方法，以减轻酗酒导致的记忆障碍。行为训练技术是基于从一种情况转移到另一种情况的，而药理学治疗将包括急性施用胆碱酯酶抑制剂或慢性胆碱补充剂以对后代的饮食。总的来说，这些研究将进一步理解我们对使用FAS或ARND观察到的记忆障碍的理解，或者使用具有动物模型的任务，而动物模型不在显式空间学习和记忆的范围内。使用行为和药理学策略同时改善这些认知缺陷的潜力将提供有关受苦个体治疗方法的重要信息。