CHRONIC POSTNATAL ALCOHOL AND ATTENTION IN THE RAT

在酒精相关出生缺陷(ARBD)的动物研究中，缺乏对酒精引起的基本注意机制变化的系统分析。这项拟议的研究将采用定向反应的测量方法，定向反应是由新刺激引起的中枢、自主神经和行为反应的集合，被认为是动物和人类注意的中心过程的索引。这项拟议研究的长期目标是严格调查注意力的基本衡量标准，并在ARBD动物模型中确定它们与注意力缺陷的关系。众所周知，ARBD人类婴儿在其中一些反应的表达方面存在障碍，进一步了解这些措施最终可能被证明是对后来注意力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，该程序已被有效地用于研究与ARBD相关的神经解剖学变化。从出生后第4天到第9天，动物将被灌胃酒精。在所有这些实验中，暴露于酒精的大鼠将与假插管或仅处理的对照组进行比较。第一个实验将包括在第9天测量血液和大脑酒精水平，包括慢性酒精组和急性接触组的受试者。该设计允许评估代谢对乙醇的耐受性，并将提供有关酒精水平的信息--酒精致畸效应的一个重要决定因素。第二个实验将检测出生后酒精暴露对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是副交感神经节活动的变化。本实验将研究乙醇可能引起的基线自主神经调节的变化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酒精在断奶前动物对嗅觉和听觉刺激的反应、习惯化和短期保持方面的缺陷。有报道称，Fas/ARBD婴儿的反应习惯性和短期再认记忆存在缺陷。通过系统地评估定向反应、习惯化和保持，将对这些反应以及它们是如何被Fas/ARBD影响获得更全面的理解。

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.