PSYCHOPHARMACOLOGY OF ETHANOL-INDUCED TERATOGENESIS

乙醇致畸的心理药理学

• 批准号: 2043555
• 负责人: JOHN HENRY HANNIGAN
• 金额: $ 19.14万
• 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 1996-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2043555
• 关键词: acetylcholine; age difference; alcoholic beverage consumption; alpha adrenergic agent; amphetamines; attention deficit disorder; central nervous system disorders; central nervous system stimulants; child behavior disorders; child mental disorders; cholinergic agents; clonidine; developmental neurobiology; disease /disorder model; dopamine; dopamine receptor; ethanol; fetal alcohol syndrome; gender difference; laboratory rat; learning; limbic system; memory; methylphenidate; neurochemistry; neurotransmitters; norepinephrine; psychopharmacology; psychotropic drugs; teratogens

Children of women who drink alcohol during their pregnancies can have facial anomalies, growth retardation, and wide-ranging central nervous system (CNS) dysfunction(s). These attentional, cognitive and behavioral problems are the most common and persistent Alcohol-Related Birth Defects (ARBDs). Although Fetal Alcohol Syndrome (FAS) and ARBDs are thought to be the most common theoretically preventable causes of developmental disabilities in the Western world, little, if any, systematic information is available on treatment for FAS/ARBDs. This project will use a valid rodent model of ARBDs to study psychopharmacological responses to CNS stimulants - drugs used to treat hyperactivity and attentional deficits in children. The proposed research will test the ability of, for example, Ritalin, Dexadrine and Cylert to attenuate the effects of in utero alcohol exposure on hyperactivity, attention, and learning and memory in rats. The proposed studies will expand upon our previous work showing altered responses to drugs acting on CNS dopamine neurotransmitter systems. Specifically, we will use rats exposed prenatally to alcohol to assess age- and gender- influenced: 1. Behavior in tasks sensitive to attentional dysfunction; 2. Attenuation of behavioral, attentional and cognitive deficits with CNS stimulants; and 3. Changes in the functional status of specific components of CNS dopamine systems - systems which mediate the therapeutic action of the CNS stimulants. The results of the proposed studies will indicate the ability of CNS stimulants to attenuate some of the behavioral sequelae of prenatal alcohol exposure. Challenges with selective dopaminergic drugs will also indicate the nature and site of specific CNS changes that may underly these deficits. Finally, these studies will facilitate attaining our long-term goal to identify potential pharmacological treatments for children with FAS/ARBDs.

怀孕期间饮酒的妇女的孩子可能会患上 面部异常、生长迟缓和广泛的中枢神经 系统（CNS）功能障碍。 这些注意力、认知和行为 问题是最常见和持续存在的与酒精相关的出生缺陷 （ARBD）。 尽管胎儿酒精综合症 (FAS) 和 ARBD 被认为 是最常见的理论上可预防的发育原因 西方世界的残疾人，系统信息很少（如果有的话） 可用于 FAS/ARBD 治疗。 该项目将使用有效的 ARBD 啮齿动物模型来研究 对中枢神经系统兴奋剂的精神药理学反应 - 用于治疗的药物 儿童多动症和注意力缺陷。 拟议的 研究将测试利他林（Ritalin）、地塞君（Dexadrine）和 Cylert 可减轻子宫内酒精暴露对胎儿的影响 大鼠的多动症、注意力以及学习和记忆。 拟议的 研究将扩展我们之前的工作，显示对 作用于中枢神经系统多巴胺神经递质系统的药物。 具体来说，我们 将使用产前暴露于酒精的老鼠来评估年龄和性别 影响： 1. 对注意力功能障碍敏感的任务中的行为； 2. 减轻行为、注意力和认知缺陷 中枢神经系统兴奋剂；和 3.中枢神经系统特定成分功能状态的变化 多巴胺系统 - 介导多巴胺治疗作用的系统 中枢神经系统兴奋剂。 拟议研究的结果将表明中枢神经系统的能力 兴奋剂可减轻产前的一些行为后遗症 酒精暴露。 选择性多巴胺能药物的挑战也将 表明可能潜在的特定中枢神经系统变化的性质和部位 这些赤字。 最后，这些研究将有助于实现我们的目标 长期目标是确定潜在的药物治疗方法 患有 FAS/ARBD 的儿童。