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.

女性可卡因滥用者在怀孕期间多次吸毒是很常见的。 据估计，85%的怀孕可卡因吸毒者也吸烟； 酒精、大麻、安非他明和镇静剂的使用量减少 在怀孕的前三个月和第三个三个月之间，烟草使用不会。尽管 对于它们联合使用的频率，还没有系统的研究 产前可卡因和尼古丁暴露的影响。但是，使用这两种方法之一 怀孕期间单独服用药物与妊娠并发症有关， 发育受损和轻微的行为异常，母亲吸烟是 也是长期智力损害的标志变量。 拟议中的研究将确定产前的行为后遗症 接触可卡因和尼古丁，无论是单独接触还是联合接触 用我们实验室开发的大鼠模型生下的后代。在工作中 假说是发育中的大脑暴露在非致畸环境中 剂量的这些药物将扰乱结构和功能 中枢神经系统的组织，这反过来将改变 后代。该模型包括每天皮下给药20 妊娠时通过渗透压泵注射可卡因和/或尼古丁5 mg/kg 第8天至第21天成对供水和盐水处理的水坝都将服务于 作为对照。血浆中可卡因、尼古丁及其主要成分的水平 代谢物将在GD15的母体和幼崽中进行测定 出生；将在几个大脑区域检测多巴胺和DOPAC水平 在不同年龄的后代中。采用分体产仔设计，雄性和 来自5个产前治疗条件的女性将在 各种行为范式。纵向(从1周到15个月 年龄段]方法将用于：1)确定行为领域 (认知、情绪/动机和运动)受产前可卡因影响 和尼古丁暴露；2)确定联合药物暴露 单独加重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心率的延迟 发展，后来出现的功能能力的变化 成人，或导致早衰；以及4)评估 可能产生特定于性别的影响。 这些实验将提供一些关于 产前暴露于可卡因和/或尼古丁对男性和 雌性后代，并应该开始建立关于 孕期接触铅引起的行为异常的性质 这两种药。大量行为测试的使用，以及 产前暴露窗口和最常用药物剂量的选择 将允许复制和扩展几个 实验室和促进解决相互矛盾的研究结果 关于产前单独接触任何一种药物的影响。作为 目标行为也反映出认知和/或表现上的缺陷 在临床文献中报道，这项研究的结果可能 可作为确定联合使用的相对风险的指南 这两种药物在怀孕期间传给后代。身份的鉴定 作为长期和受影响领域的暂时性赤字可能会影响 治疗方案的选择。