PSYCHOPHARMACOLOGY OF ETHANOL-INDUCED TERATOGENESIS

乙醇致畸的心理药理学

• 批准号: 3110028
• 负责人: JOHN HENRY HANNIGAN
• 金额: $ 18.47万
• 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/3110028
• 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; 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.

怀孕期间喝酒的妇女的孩子可以 面部异常，增长迟钝和广泛的中枢神经 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与酒精有关的先天缺陷 （arbds）。 尽管认为胎儿酒精综合征（FAS）和ARBD 成为理论上最常见的发展原因 西方世界的残疾，很少（如果有的话）系统信息 可用于FAS/ARBD的治疗。 该项目将使用有效的ARBD啮齿动物模型来研究 心理药理学对中枢神经系统兴奋剂的反应 - 用于治疗的药物 儿童的多动症和注意力缺陷。 提议 研究将测试例如利他林，右旋水和 旋风减轻子宫酒精暴露对子宫的影响 大鼠的多动症，注意力以及学习和记忆。 提议 研究将扩大我们以前的工作，显示对 作用于CNS多巴胺神经递质系统的药物。 具体来说，我们 将在产前暴露于酒精的大鼠评估年龄和性别 受影响： 1。任务中对注意力障碍敏感的行为； 2。行为，注意力和认知缺陷的衰减 中枢神经系统兴奋剂；和 3。CNS特定组件的功能状态的变化 多巴胺系统 - 介导的系统 中枢神经系统兴奋剂。 拟议的研究结果将表明中枢神经系统的能力 刺激物减轻产前的某些行为后遗症 酒精暴露。 选择性多巴胺能药物的挑战也将 指示可能基本的特定CNS变化的性质和位点 这些赤字。 最后，这些研究将有助于达到我们的 长期目标以确定潜在的药理治疗 患有FAS/ARBD的孩子。