NEUROBEHAVIORAL TERATOGENIC INVESTIGATIONS OF COCAINE

可卡因的神经行为致畸研究

• 批准号: 2377356
• 负责人: LINDA PATIA SPEAR
• 金额: $ 16.93万
• 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 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2377356
• 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研究 早期可卡因暴露的神经行为后果。 最大的两个 在上一个项目期间观察到的强大行为改变 在Sprague-Dawley大坝的后代，皮下暴露于可卡因 从妊娠日8-20，相对于配对的后代和 未经处理的控制大坝是； （a）他们对 压力源和（b）它们在复合物中表现出的认知缺陷 大概是压力的测试情况。 明显的衰减 在某些反应措施上观察到多巴胺（DA）活性，但没有 其他，导致假设，潜在的DA缺陷可能 在基础下的神经补偿过程在功能上应对 条件，但在具有挑战性或压力的测试下可能会“揭露” 情况。 本提案中概述的工作将检查 这两种类型的可卡因暴露后代的改变 “挑战”，重点是DA功能的可能改变 为这些长期行为后果造成了因素 妊娠可卡因暴露。 实验系列1将检查 成人后代对急性应激源的行为反应。 暴露于可卡因及其行为，神经化学和 激素对急性和重复应激源的反应。 这些意图 研究是为了评估行为反应的方式 应力源已通过产前可卡因暴露而改变，并确定 是否使用使用类似的压力反应性改变 激素和神经化学反应措施，特别重点 在评估DA反应性改变的后者中 压力源的系统。 实验系列2将进一步关注 这些后代的行为评估。 最初的研究 系列将检查成年可卡因暴露的后代是否不展示 仅在逆转性能中缺陷，但其他行为的改变 与DA末端区域的破坏有关的。 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 过程导致它们在认知表现方面的改变。 在这个 研究的早期研究 可卡因，这种动物研究对于确认和扩展至关重要 潜在混淆临床发现，以期待其他潜力 早期可卡因暴露的后果，并提供见解 影响大量发展结果的机制 在产前暴露于这种虐待药物的儿童中。