PSYCHOPHARMACOLOGY OF ETHANOL-INDUCED TERATOGENESIS

乙醇致畸的心理药理学

• 批准号: 3110031
• 负责人: JOHN HENRY HANNIGAN
• 金额: $ 9.19万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3110031
• 关键词: acetylcholine; alcoholic beverage consumption; alcoholism /alcohol abuse; alpha adrenergic agent; amphetamines; anticholinergic agent; apomorphine; arecoline; attention deficit disorder; central nervous system disorders; centrally acting drug; child behavior disorders; child mental disorders; cholinergic agents; clonidine; dopamine; dopamine receptor; ethanol; fetal alcohol syndrome; haloperidol; laboratory rat; methylphenidate; neurochemistry; neurotransmitters; norepinephrine; phentolamine; psychopharmacology; psychotropic drugs; scopolamine; teratogens; tranquilizer

Children born of mothers who drink alcohol during their pregnancies can be afflicted with syndrom of morphological anomolies of varying severity and of behavioral dysfunctions ranging from profound mental retardation to hyperactivity to subtler marginal deficits. The behavioral effects of prenatal alcohol exposure in children have been modeled reliably by administrating pregnant rats liquid diets containing different percentages of ethanol-derived calories (35% or 0% EDC). The model produces pups in which maturational delays and deficits in activity and learning have been studied successfully. The biological, and in particular, neurochemical bases for the behavioral effects of prenatal alcohol exposure are not well understood. We intend to investigate the functional integrity of central nervous system neurotransmitter systems in these animals by measuring the development of their behavioral responses to pharmacological agents. Specifically, our aim is to study the influence of prenatal alcohol exposure on behaviroal responses to drugs which influence dopamine, norepinephrine and acetylcholine systems. In particular, the pharmacological treatments chosen will be used because they are known to influence various measures of locomotor activity, display well-defined developmental courses, and have relatively well-understood mechanisms of action. The results of the proposed experiments, first, will provide important information with which to characterize the functional effects of prenatal alcohol exposure on neurotransmitter systems. Secondly, results which show attenuated behavioral effects of prenatal alcohol exposure in the animal model may suggest possible therapeutic treatments for children with symptoms of fetal alcohol exposure. Thirdly, these pharmacological challenges may reveal subtle or marginal deficits and thereby may prove useful in determining the range of influence of prenatal alcohol exposure. In summary, the proposed experiments will utilize a reliable animal model of the behavioral effects of prenatal alcohol exposure in children to study the symptomatic contribution and funcitonal integrity of neurotransmitter systems in "Fetal Alcohol Syndrome." The nature and developmental course of specific psychopharmacological responses wil be tested. The results of this research will provide important information on the developmental courses of specific behaviors after prenatal alcohol exposure, on the nature of relatively specific neurotransmitter involvement in the behavioral changes, and on the possible diagnostic and therapeutic uses of these pharmacological challenges.

在怀孕期间喝酒的母亲所生的孩子可以是 患有不同严重程度和 行为功能障碍，从深刻的智力低下到 对微妙的边缘缺陷的多动症。 行为影响 儿童的产前酒精暴露已通过 管理怀孕的大鼠液体饮食，包含不同百分比 乙醇衍生的卡路里（35％或0％EDC）。 该模型在 哪些成熟的延误和活动缺陷已经 成功学习。 生物学，特别是神经化学 产前酒精暴露的行为影响的基础不好 理解。 我们打算研究中央的功能完整性 通过测量这些动物的神经系统神经递质系统 他们对药理剂的行为反应的发展。 具体而言，我们的目的是研究产前酒精的影响 对影响多巴胺的药物的行为反应暴露， 去甲肾上腺素和乙酰胆碱系统。 特别是 选择的药理治疗将被使用，因为它们已知 影响运动活动的各种措施，表现明确 发展课程，并具有相对良好的机制 行动。 提议的实验的结果首先将提供 重要信息以表征的功能效应 神经递质系统上的产前酒精暴露。 其次，结果 这表明产前酒精暴露的行为影响减弱 动物模型可能建议对儿童进行治疗 胎儿酒精暴露的症状。 第三，这些药理学 挑战可能揭示出细微或边际赤字，从而证明 用于确定产前酒精暴露的影响范围。 总而言之，拟议的实验将利用可靠的动物模型 儿童中酒精暴露的行为影响 神经递质的症状贡献和funcitonal完整性 “胎儿酒精综合征”的系统。 自然和发展课程 将测试特定的心理药理反应。 结果 这项研究将提供有关发展的重要信息 产前酒精暴露后的特定行为课程， 相对特异的神经递质参与的性质 行为改变，以及可能的诊断和治疗用途 这些药理挑战。