ALCOHOL-INDUCED BEHAVIORAL TERATOGENESIS

酒精诱发的行为致畸

• 批准号: 3479867
• 负责人: EDWARD P RILEY
• 金额: $ 21.71万
• 依托单位: SAN DIEGO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3479867
• 关键词: alcoholic beverage consumption; alcoholism /alcohol abuse; aspirin; avoidance behavior; behavior; behavior disorders; behavior test; congenital nervous system disorder; dosage; drug interactions; embryo /fetus toxicology; enzyme inhibitors; enzyme mechanism; ethology; exploratory behavior; fetal alcohol syndrome; infant animal; inhibitor /antagonist; laboratory rat; learning disorders; longitudinal animal study; maternal behavior; memory disorders; neuroanatomy; neuroendocrine system; play; prenatal stress; prostaglandin endoperoxide synthase; prostaglandins; psychomotor disorders; psychomotor reaction time; psychopharmacology

Although a considerable amount of data has been published regarding the morphological and behavioral effects associated with prenatal alcohol exposure, very little information is known regarding the underlying mechanisms for these effects. Recently, alcohol's interaction with the prostaglandins has been implicated as one possible mechanism for some of the consequences associated with alcohol exposure in utero. Support for this hypothesis stems from studies showing that pretreatment with the prostaglandin synthetase inhibitors, aspirin and indomethacin, prior to alcohol exposure reduces fetal hypoplasia and the incidence of fetal death and malformations in mice. In this proposal, we plan to look at the role of prostaglandins in some of the behavioral and physiological effects that are found following prenatal alcohol exposure. In the first set of experiments, we will examine the effects of aspirin pretreatment will ameliorate some of the effects associated with prenatal alcohol exposure. In the first set of experiments, we will examine the effects of aspirin pretreatment will ameliorate some of the effects associated with prenatal alcohol exposure. In the first set of experiments, we will examine the effects of aspirin pretreatment and acute and chronic alcohol exposure on fetal movement, since alcohol exposure has been shown to result in a suppression of fetal movement. Also, reduced fetal movement has been suggested as one possible cause for some of alcohol's morphological effects. In the second series of experiments, we will examine the effects of aspirin pretreatment on sexually dimorphic behaviors and neuroanatomical structures that have been shown to be sensitive to prenatal alcohol exposure. The arachidonic acid cascade, which results in the production of prostaglandins, has been implicated in some of the effects of testosterone during fetal development and thus, may play a role in some of the alcohol-related changes in sexually dimorphic behaviors that have been reported. In the third series of experiments, the effects of aspirin pretreatment on a number of behaviors that are known to be sensitive to prenatal alcohol exposure will be examined to determine if this pretreatment can ameliorate some of the behavioral dysfunctions that are typically associated with prenatal alcohol exposure.

尽管已经公布了大量有关 与产前酒精相关的形态和行为影响 暴露，关于底层的信息知之甚少 这些影响的机制。最近，酒精与 前列腺素被认为是某些疾病的一种可能机制 与子宫内酒精暴露相关的后果。支持 这一假设源于研究表明，用 前列腺素合成酶抑制剂、阿司匹林和吲哚美辛，之前 酒精暴露会降低胎儿发育不全和胎儿畸形的发生率 小鼠死亡和畸形。在本提案中，我们计划考虑 前列腺素在某些行为和生理方面的作用 产前接触酒精后发现的影响。在第一个 一组实验，我们将检查阿司匹林预处理的效果 会改善与产前酒精相关的一些影响 接触。在第一组实验中，我们将检查以下效果： 阿司匹林预处理将改善与以下相关的一些影响 产前酒精暴露。在第一组实验中，我们将 检查阿司匹林预处理以及急性和慢性酒精的影响 暴露对胎动的影响，因为酒精暴露已被证明 导致胎动受到抑制。另外，胎动也减少了 已被认为是某些酒精中毒的可能原因之一 形态效应。在第二个系列的实验中，我们将 检查阿司匹林预处理对性二态性的影响 行为和神经解剖结构已被证明 对产前酒精暴露敏感。花生四烯酸级联， 导致前列腺素的产生，与 睾酮在胎儿发育过程中的一些影响，因此， 可能在一些与酒精相关的性变化中发挥作用 已报道的二态性行为。在第三个系列中 实验，阿司匹林预处理对多种行为的影响 已知对产前酒精暴露敏感的人将 检查以确定这种预处理是否可以改善某些 通常与产前相关的行为功能障碍 酒精暴露。