NEUROBEHAVIORAL TERATOGENIC INVESTIGATIONS OF COCAINE

可卡因的神经行为致畸研究

• 批准号: 2117215
• 负责人: LINDA PATIA SPEAR
• 金额: $ 16.4万
• 依托单位: STATE UNIVERSITY OF NY,BINGHAMTON
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-09-01 至 2000-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2117215
• 关键词: animal developmental psychology; behavior test; cocaine; cognition; developmental neurobiology; dopamine; embryo /fetus toxicology; environmental adaptation; hormone regulation /control mechanism; laboratory rat; neurochemistry; neuropsychology; performance; prenatal stress; psychopharmacology; stressor

The work outlined in this proposal will examine further the neurobehavioral consequences of early cocaine exposure. Two of the most robust behavioral alterations observed during the previous project period in offspring of sprague-Dawley dams exposed subcutaneously to cocaine from gestational days 8-20, relative to offspring of pair-fed and untreated control dams, were; (a) their unusual behavioral response to stressors and (b) the cognitive deficits they exhibit in complex or presumably stressful testing situations. Apparent attenuations in dopamine (DA) activity were observed on some response measures, but not others, leading to the hypothesis that the underlying DA deficiency may be functionally countered by neural compensatory processes under basal conditions, but may be "unmasked" under challenging or stressful test circumstances. The work outlined in this proposal will examine the alterations in cocaine-exposed offspring under these two types of "challenges," with an emphasis on possible alterations in DA function as contributing factors to these long-term behavioral consequences of gestational cocaine exposure. Experimental Series 1 will examine the behavioral responses to acute stressors in adult offspring prenatally exposed to cocaine as well as their behavioral, neurochemical and hormonal response to acute and repeated stressors. The intent of these studies is to evaluate in what ways the behavioral responsivity to stressors has been altered by prenatal cocaine exposure, and to determine whether similar alterations in stress responsivity are seen using hormonal and neurochemical response measures, with a particular emphasis in the latter on assessment of alterations in responsiveness of the DA systems to stressors. Experimental Series 2 will focus further on behavioral assessments in these offspring. The first studies in this series will examine whether adult cocaine-exposed offspring exhibit not only deficits in reversal performance, but alterations in other behaviors that have been associated with disruption of DA terminal regions. The second part of this series will examine in more detail the cognitive alterations in these offspring by assessing what behavioral features and processes lead to their alterations in cognitive performance. At this early stage in the investigation of the developmental toxicology of cocaine, such animal research is critical to confirm and extend potentially confounded clinical findings, to anticipate other potential consequences of early cocaine exposure, as well as to offer insights into the mechanisms influencing the developmental outcome of the large number of children that have been exposed prenatally to this drug of abuse.

本提案中概述的工作将进一步审查 早期接触可卡因的神经行为后果。 其中两个最 在上一个项目期间观察到的强烈行为改变 皮下接触可卡因的斯普拉格-道利水坝的后代 从妊娠第 8 天到 20 天，相对于配对喂养和 未经处理的对照水坝； (a) 他们不寻常的行为反应 压力源和（b）他们在复杂或复杂的情况下表现出的认知缺陷 大概是压力测试情况。 明显的衰减 在一些反应措施中观察到多巴胺 (DA) 活性，但没有观察到 其他，导致假设潜在的 DA 缺乏可能 在基础条件下通过神经补偿过程在功能上抵消 条件下，但在具有挑战性或压力的测试下可能会“暴露” 情况。 本提案中概述的工作将审查 在这两种类型下，暴露于可卡因的后代的变化 “挑战”，重点是 DA 功能可能发生的改变 造成这些长期行为后果的因素 妊娠期可卡因暴露。 实验系列 1 将检查 成年后代产前对急性应激源的行为反应 接触可卡因以及他们的行为、神经化学和 对急性和反复压力源的荷尔蒙反应。 这些的意图 研究的目的是评估行为反应的方式 产前接触可卡因改变了压力源，并确定 是否可以看到压力反应性的类似变化 激素和神经化学反应措施，特别强调 后者是对 DA 反应性变化的评估 系统对压力源的影响。 实验系列 2 将进一步关注 对这些后代的行为评估。 这方面的第一个研究 系列将检查成年暴露于可卡因的后代是否表现出不 仅逆转表现存在缺陷，但其他行为发生改变 这与 DA 终端区域的破坏有关。 这 本系列的第二部分将更详细地研究认知 通过评估哪些行为特征和 过程导致他们认知表现的改变。 在此 发育毒理学研究的早期阶段 可卡因，此类动物研究对于确认和扩展至关重要 可能混淆的临床结果，以预测其他潜在的 早期接触可卡因的后果，并提供见解 影响多数人发展结果的机制 产前接触过这种滥用药物的儿童。