NEUROBEHAVIORAL EFFECTS OF PRENATAL COCAINE AND NICOTINE EXPOSURE

产前接触可卡因和尼古丁对神经行为的影响

• 批准号: 6494799
• 负责人: Sonya K Sobrian
• 金额: $ 13.19万
• 依托单位: HOWARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6494799
• 关键词: 3,4 dihydroxyphenylacetate; association learning; avoidance behavior; behavior test; behavioral /social science research tag; behavioral habituation /sensitization; cocaine; cognition disorders; developmental neurobiology; dopamine; drug abuse; embryo /fetus toxicology; gender difference; laboratory rat; longitudinal animal study; mood disorders; motivation; neuromuscular function; nicotine; prenatal stress; statistics /biometry; substance abuse related behavior; tobacco abuse

Multiple drug use among female cocaine abusers is common during pregnancy. Estimates are that 85% of pregnant cocaine users also smoke cigarettes; while use of alcohol, marijuana, amphetamine an tranquilizers decreases between the first and third trimesters, tobacco use does not. Despite the frequency of their combined use, there has been no systematic study of the effects of prenatal cocaine and nicotine exposure. However, use of either drug alone during pregnancy is linked with pregnancy complications, impaired growth and subtle behavioral abnormalities, maternal smoking is also a marker variable for long-term intellectual impairment. The proposed research will determine the behavioral sequelae of prenatal exposure to cocaine and nicotine, either alone or in combination, in offspring using a rat model developed in our laboratory. The working hypothesis is that exposure of the developing brain to non-teratogenic doses of these drugs will disrupt the structural and functional organization of the CNS, which in turn will alter behavior in the offspring. The model involves the daily subcutaneous administration of 20 mg/kg of cocaine and/or 5 mg/kg of nicotine by osmotic pump on gestation days (GD) 8 through 21. Both pair-fed and saline-treated dams will serve as controls. Plasma levels of cocaine, nicotine and their major metabolites will be determine in dams on GD 15 and mothers and pups at birth; dopamine and DOPAC levels will be assayed in several brain region in offspring at various ages. Using a split-litter design, males and females from the 5 prenatal treatment conditions will be tested in a variety of behavioral paradigms. A longitudinal (from 1 week to 15 months of age] approach will be used to: 1) identify the behavioral domains (cognitive, emotional/motivational and motor) affected by prenatal cocaine and nicotine exposure; 2) determine whether combined drug exposure exacerbates or ameliorates the behavioral effects of either drug alone; 3) investigate whether these changes represent a delay in the rat of development, a later appearing alteration in functional capacity of the adult, or an induction of premature senescence; and 4) assess the possibility of gender-specific effects. These experiments will provide some of the first longitudinal data on the effects of prenatal exposure to cocaine and/or nicotine on both male and female offspring, and should begin to establish a consensus about the nature of the behavioral abnormalities produce by gestational exposure to these two drugs. The use of a large battery of behavioral tests, and the choice of the prenatal exposure window and drug doses most frequently used will allow for the replication and extension of the work of several laboratories and facilitate the resolution of conflicting findings regarding the effects of prenatal exposure to either drug alone. As the behaviors targeted also reflect cognitive and/or performance deficits reported in the clinical literature, the outcome of this research may serve as a guideline for determining the relative risks of combined use of these two drugs during pregnancy to the offspring. The identification of deficits as transient of long-term and the domains affected may impact the choice of treatment options.

在怀孕期间，女性可卡因滥用者中多种药物使用是常见的。 估计有85％的怀孕可卡因使用者也抽烟。 在使用酒精，大麻，苯丙胺和镇静剂时减少 在第一个和第三个三体之间，烟草的使用情况却没有。尽管有 他们合并使用的频率，没有系统的研究 产前可卡因和尼古丁暴露的影响。但是，使用任何一个 仅怀孕期间的药物与怀孕并发症有关， 生长受损和微妙的行为异常，孕产妇的吸烟是 也是长期智力障碍的标记变量。 拟议的研究将确定产前的行为后遗症 单独或组合接触可卡因和尼古丁 使用我们实验室中开发的大鼠模型的后代。工作 假设是发育中的大脑暴露于非致病性 这些药物的剂量会破坏结构和功能 中枢神经系统的组织将改变 后代。该模型涉及每天的皮下给药20 可卡因毫克/千克可卡因和/或5 mg/kg尼古丁通过妊娠渗透泵 天（GD）8至21。配对和盐水处理的水坝都将服务 作为控件。可卡因，尼古丁及其主要的血浆水平 代谢物将在GD 15的大坝中确定，母亲和幼崽在 出生；多巴胺和多巴糖水平将在几个大脑区域进行测定 在各个年龄的后代。使用拆分式设计，男性和 来自5个产前治疗条件的女性将在A中测试 各种行为范式。纵向（从1周到15个月 年龄]方法将用于：1）确定行为域 （认知，情感/动机和运动）受产前可卡因影响 和尼古丁的暴露； 2）确定是否合并药物暴露 加剧或改善任何一种药物的行为影响； 3） 调查这些变化是否代表大鼠的延迟 开发，后来出现在功能能力的变化 成人，或过早衰老的诱导； 4）评估 性别特异性影响的可能性。 这些实验将提供有关该实验的一些第一个纵向数据 产前暴露于可卡因和/或尼古丁对男性和尼古丁的影响 女性后代，应该开始建立关于 行为异常的性质是通过妊娠暴露而产生的 这两种药物。使用大量的行为测试，以及 选择产前暴露窗口和最常用的药物剂量 将允许复制和扩展几个 实验室并促进解决相互矛盾的发现 关于单独暴露于两种药物的影响。作为 针对目标的行为还反映了认知和/或表现不足 在临床文献中报道，这项研究的结果可能 作为确定合并使用相对风险的指南 怀孕期间的这两种药物。识别 作为长期瞬态和受影响的域的赤字可能会影响 选择治疗选择。