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改变的系统分析。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、自主和行为反应的集合，被认为是动物和人类注意力中心过程的索引。该研究的长期目标是严格调查注意力的基本指标，并确定它们与ARBD动物模型中的注意力缺陷之间的关系。已知ARBD人类婴儿在这些反应中的一些表达受损，进一步了解这些措施可能最终被证明是新生儿诊断后期注意力功能障碍的一部分。这些实验将利用产后酒精给药程序，该程序已有效地用于研究与ARBD相关的神经解剖学变化。从出生后第4天到第9天，将给动物灌胃酒精。在所有这些实验中，暴露于乙醇的大鼠将与对照组进行比较，对照组要么是假插管，要么只是处理。第一个实验将包括在第9天测量慢性乙醇组和急性酒精暴露组的血液和大脑酒精水平。该设计允许评估对乙醇的代谢耐受性，也将提供关于达到的酒精水平的信息，这是酒精致畸作用的一个重要决定因素。第二个实验将检查出生后酒精暴露对12和16日龄自主神经系统（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分裂活动的变化。本实验将检验乙醇可能引起的基线自主调节的改变，以及心脏对一种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和短期保留的缺陷。在FAS/ARBD婴儿中有反应习惯和短期识别记忆缺陷的报道。通过系统地评估定向反应、习惯和保持，将更全面地了解这些反应以及它们如何受到FAS/ARBD的影响。

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.