Developmental consequences of in utero cocaine

子宫内可卡因的发育后果

• 批准号: 7056322
• 负责人: BARBARA L THOMPSON
• 金额: $ 4.88万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056322
• 关键词: cocaine; interneurons; receptor

DESCRIPTION (provided by applicant): Prenatal cocaine exposure during critical periods of development in rabbits selectively alters the structure of specific types of neurons and the coupling of the D1 dopamine (DA) receptor in DA-rich regions of the cerebral cortex, such as prefrontal and anterior cingulate cortices. Consistent with findings in this model system, children exposed to cocaine in utero exhibit a developmental phenotype that resembles attention deficit disorder. The specific expression patterns of the D1 receptor, changes in neurophysiological properties of cortical interneurons modulated by DA, and disrupted attention will be investigated in the rabbit model of in utero cocaine exposure. Pharmacological manipulations will establish a direct role of D1 receptor dysfunction in the poor performance on tasks that tap attention systems. Preliminary data suggest that in utero cocaine results in systems that function normally at baseline, but when the system is challenged, behavioral abnormalities emerge. Detailed characterization of the developmental consequences of prenatal cocaine exposure in this animal model will facilitate an understanding of the underlying molecular and cellular mechanisms that disrupt behavior in the clinical population.

描述（由申请人提供）： 兔子在发育关键时期的产前接触可卡因会选择性地改变特定类型神经元的结构以及大脑皮层富含 DA 区域（例如前额叶和前扣带皮层）中 D1 多巴胺 (DA) 受体的偶联。与该模型系统中的发现一致，在子宫内接触可卡因的儿童表现出类似于注意力缺陷障碍的发育表型。 D1 受体的特定表达模式、DA 调节的皮质中间神经元的神经生理学特性的变化以及注意力障碍将在子宫内可卡因暴露的兔子模型中进行研究。药理学操作将确定 D1 受体功能障碍在注意力系统任务表现不佳中的直接作用。初步数据表明，子宫内可卡因会导致系统在基线时正常运行，但当系统受到挑战时，就会出现行为异常。在该动物模型中详细描述产前可卡因暴露的发育后果将有助于了解破坏临床人群行为的潜在分子和细胞机制。