PRENATAL COCAINE EXPOSURE AND ATTENTIONAL DYSFUNCTION

产前接触可卡因和注意力功能障碍

• 批准号: 6858753
• 负责人: BARBARA J STRUPP
• 金额: $ 49.86万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-06-01 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6858753
• 关键词: G protein; attention deficit disorder; autoradiography; behavior test; behavioral /social science research tag; catecholamines; cingulate gyrus; cocaine; congenital disorders; dopamine receptor; drug abuse; embryo /fetus toxicology; female; laboratory rat; mother /embryo /fetus nutrition; neurochemistry; prefrontal lobe /cortex; receptor coupling

DESCRIPTION (Adapted from applicant's abstract): Using a clinically relevant animal model, the applicants' studies have revealed that rats exposed to cocaine prenatally (IV) exhibit a selective impairment in two aspects of attentional function, whereas many other cognitive functions appear spared. The proposed studies are designed to test the hypothesis that: The type of attentional impairment seen following prenatal cocaine exposure results from alterations in catecholaminergic systems in prefrontal cortex (PFC) and/or anterior cingulate cortex (ACC), and that the targeting of these systems with potential therapeutic agents will ameliorate the attentional impairments. In the first set of studies, they will assess various attentional functions as well as the functional integrity of frontal dopaminergic (DA) and noradrenergic (NE) systems in the same animals. For the NE system, they will measure the density of alpha1 and alpha2 adrenoreceptors and NE transporter in PFC and ACC (and control regions). Similarly, the functional integrity of DA circuitry in ACC and PFC will be assessed by measures of D1, D2, and D3 receptor density, the DA transporter, and coupling of D1 and D2 receptors to their associated G proteins. In addition to providing new information about the effects of prenatal cocaine exposure on attentional function and on NE and DA systems in frontal cortex, these studies provide a unique opportunity to establish functional relationships between observed cognitive and neural changes. This is not possible with the more common approach of assessing behavioral and neural changes in separate groups of animals, often exposed to cocaine via different routes and doses, with very different handling and testing histories. In the second set of experiments, the efficacy of putative therapeutic agents will be examined. These studies will: (a) provide direct tests of putative links suggested by the first set of experiments and (b) identify drugs that are likely to be useful therapeutically. A final contribution of both sets of studies is to further elucidate the roles of the PFC and ACC and their catecholaminergic innervation in cognitive functioning. The use of tasks that specifically tap various attentional functions (including in-depth analyses of performance data), coupled with assessment of putative neural mechanisms in the same animals, should provide new information concerning the roles of these systems.

描述（改编自申请人的摘要）：使用临床相关的 动物模型中，申请人的研究表明，暴露于 产前（IV）可卡因在两个方面表现出选择性损伤 注意力功能，而许多其他认知功能似乎幸免于难。这 拟议的研究旨在检验以下假设： 产前接触可卡因后出现的注意力障碍是由于 前额皮质（PFC）和/或儿茶酚胺能系统的改变 前扣带皮层（ACC），并且这些系统的目标 潜在的治疗药物将改善注意力障碍。在 在第一组研究中，他们将评估各种注意力功能 以及额叶多巴胺能 (DA) 和去甲肾上腺素能的功能完整性 （NE）系统在同一动物中。对于NE系统，他们将测量 PFC 和 ACC 中 α1 和 α2 肾上腺素受体以及 NE 转运蛋白的密度 （和控制区域）。同样，DA 电路的功能完整性 ACC 和 PFC 将通过测量 D1、D2 和 D3 受体密度来评估， DA 转运蛋白，以及 D1 和 D2 受体与其相关 G 的偶联 蛋白质。除了提供有关影响的新信息之外 产前可卡因暴露对注意力功能以及 NE 和 DA 系统的影响 额叶皮层，这些研究提供了一个独特的机会来建立 观察到的认知和神经变化之间的功能关系。这是 使用更常见的评估行为和神经的方法是不可能的 不同动物群的变化，通常通过不同的途径接触可卡因 途径和剂量，具有截然不同的处理和测试历史。在 第二组实验，假定的治疗剂的功效将是 检查了。这些研究将：(a) 提供对假定链接的直接测试 由第一组实验建议并（b）确定药物 可能在治疗上有用。两组的最终贡献 研究的目的是进一步阐明 PFC 和 ACC 的作用及其 认知功能中的儿茶酚胺能神经支配。使用任务 具体挖掘各种注意力功能（包括深入分析 性能数据），再加上对假定的神经机制的评估 同样的动物，应该提供有关这些作用的新信息 系统。