CHRONIC POSTNATAL ALCOHOL AND ATTENTION IN THE RAT

大鼠慢性产后酒精和注意力

• 批准号: 6040591
• 负责人: PAMELA S HUNT
• 金额: $ 6.71万
• 依托单位: COLLEGE OF WILLIAM AND MARY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6040591
• 关键词: alcoholism /alcohol abuse; attention deficit disorder; auditory stimulus; behavioral /social science research tag; behavioral habituation /sensitization; blood brain barrier; chronic disease /disorder; disease /disorder model; drug tolerance; embryo /fetus toxicology; ethanol; functional ability; heart function; infant animal; laboratory rat; model design /development; olfactory stimulus; oral administration; orientation; parasympathetic nervous system; perinatal; teratogens; tube feeding

Absent from animal research on alcohol-related birth defects (ARBD) is a systematic analysis of ethanol-induced alterations in basic attentional mechanisms. The proposed research will employ measures of the orienting response, a collection of central, autonomic, and behavioral responses elicited by novel stimuli and believed to index the central process of attention in both animals and humans. The long-term objective of the proposed research is to rigorously investigate basic measures of attention, and to determine how they relate to attentional deficits in an animal model of ARBD. ARBD human infants are known to be impaired in the expression of some of these responses, and further knowledge about these measures may ultimately prove useful as part of a neonatal diagnostic for later attentional dysfunction. These experiments will utilize a postnatal alcohol administration procedure that has been effectively used for studying neuroanatomical changes associated with ARBD. Animals will be intragastrically administered alcohol from postnatal days 4 through 9. In all these experiments ethanol-exposed rats will be compared with controls that will either be sham intubated or handled only. The first experiment will involve measuring blood- and brain-alcohol levels on day 9, both in a chronic ethanol group and in a group of acutely-exposed subjects. The design allows for the assessment of metabolic tolerance to ethanol, and will also provide information about alcohol levels achieved - an important determinant of alcohol's teratogenic effects. The second experiment will examine the effects of postnatal alcohol exposure on the functional development of the autonomic nervous system (ANS) at 12 and 16 days of age. A major component of the orienting response consists of a change in the activity of the parasympathetic division. This experiment will examine possible ethanol-induced alterations in baseline autonomic regulation as well as that of the cardiac response to a novel olfactory stimulus. The third and final experiment will assess ethanol- induced deficits in response habituation and short-term retention for both olfactory and auditory stimuli in preweanling animals. Deficits in response habituation and short-term recognition memory have been reported in FAS/ARBD infants. By systematically evaluating orienting responses, habituation and retention a fuller understanding of these responses and how they are affected by FAS/ARBD will be gained.

在酒精相关出生缺陷（ARBD）的动物研究中，缺乏对酒精诱导的基本注意力机制改变的系统分析。 拟议中的研究将采用定向反应的措施，这是一系列由新刺激引起的中枢、自主和行为反应，被认为是动物和人类注意力中枢过程的指标。 这项研究的长期目标是严格调查注意力的基本指标，并确定它们如何与ARBD动物模型中的注意力缺陷相关。 已知ARBD人类婴儿在这些反应中的一些的表达中受损，并且关于这些措施的进一步知识可能最终被证明是有用的，作为后期注意力功能障碍的新生儿诊断的一部分。这些实验将利用出生后酒精给药程序，该程序已有效用于研究与ARBD相关的神经解剖学变化。 从出生后第4天至第9天，对动物灌胃给予酒精。 在所有这些实验中，将乙醇暴露的大鼠与对照组进行比较，对照组将进行假插管或仅进行处理。 第一个实验将涉及在第9天测量血液和大脑的酒精水平，包括慢性乙醇组和急性暴露组。 该设计允许评估对乙醇的代谢耐受性，并且还将提供关于所达到的酒精水平的信息-酒精致畸作用的重要决定因素。 第二个实验将研究出生后酒精暴露对12天和16天龄自主神经系统（ANS）功能发育的影响。 定向反应的一个主要组成部分包括副交感神经分部活动的变化。 本实验将检查乙醇诱导的基线自主调节的可能改变，以及心脏对新的嗅觉刺激的反应。 第三个也是最后一个实验将评估乙醇诱导的断奶前动物对嗅觉和听觉刺激的反应、习惯化和短期保持的缺陷。在FAS/ARBD婴儿中报告了反应习惯和短期识别记忆的缺陷。 通过系统地评估定向反应，习惯化和保持，将获得对这些反应以及FAS/ARBD如何影响这些反应的更全面的理解。