Developmental consequences of in utero cocaine

描述（由申请人提供）： 在兔子发育的关键时期，产前可卡因暴露选择性地改变了特定类型神经元的结构和大脑皮层多巴胺（DA）丰富区域（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，在子宫内暴露于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受体的具体表达模式，DA调制的皮质中间神经元的神经生理学特性的变化，并中断注意力将在子宫内可卡因暴露的兔模型中进行研究。药理学操作将确定D1受体功能障碍在利用注意力系统的任务表现不佳中的直接作用。初步数据表明，在子宫内可卡因导致系统在基线时功能正常，但当系统受到挑战时，出现行为异常。详细描述产前可卡因暴露在这种动物模型中的发育后果，将有助于理解破坏临床人群行为的潜在分子和细胞机制。

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.