PRENATAL COCAINE EXPOSURE AND ATTENTIONAL DYSFUNCTION

产前接触可卡因和注意力功能障碍

• 批准号: 6711679
• 负责人: BARBARA J STRUPP
• 金额: $ 56.42万
• 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 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6711679
• 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，申请人的研究表明，暴露于 可卡因产前（IV）在两个方面表现出选择性损害 注意功能，而许多其他认知功能似乎也幸免。这 拟议的研究旨在检验以下假设： 产前可卡因暴露后观察到的注意力障碍是由 前额叶皮层（PFC）和/或 前扣带回皮层（ACC），这些系统的靶向 潜在的治疗剂将改善注意力障碍。在 第一组研究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）同一动物中的​​系统。对于NE系统，他们将测量 PFC和ACC中α1和α2肾上腺肾上腺受体和NE转运蛋白的密度 （和控制区）。同样，DA电路的功能完整性 ACC和PFC将通过D1，D2和D3受体密度的度量来评估 DA转运蛋白以及D1和D2受体与其相关G的耦合 蛋白质。除了提供有关影响的新信息 产前可卡因对注意力功能以及NE和DA系统的暴露 额叶皮层，这些研究为建立独特的机会提供了独特的机会 观察到的认知和神经变化之间的功能关系。这是 评估行为和神经的更常见方法是不可能的 单独的动物组的变化，通常通过不同的方式暴露于可卡因 路线和剂量，具有截然不同的处理和测试历史。在 第二组实验，推定治疗剂的功效将是 检查。这些研究将：（a）提供推定链接的直接测试 由第一组实验建议，（b）识别 可能在治疗上很有用。两组的最终贡献 研究是为了进一步阐明PFC和ACC的作用 认知功能中的儿茶酚胺能神经。使用任务 特别利用各种注意功能（包括对 绩效数据），加上对推定神经机制的评估 相同的动物应提供有关这些角色的新信息 系统。