Developmental consequences of in utero cocaine

兔发育关键期产前可卡因暴露选择性改变脑组织结构 脑内特定类型神经元与多巴胺(DA)受体在多巴胺(DA)富集区的偶联 大脑皮质，如前额叶和前扣带回皮质。与此模型中的研究结果一致 系统中，在子宫内暴露于可卡因的儿童表现出类似注意力的发育表型 缺乏症。D1R的特异性表达模式、神经生理学变化 多巴胺对大脑皮层中间神经元的调节和注意力中断的特性将在兔身上进行研究 宫内可卡因暴露模型。药理学操作将建立d1受体的直接作用 在利用注意力系统的任务中表现不佳的功能障碍。初步数据显示，在 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， 行为异常就会出现。产前发育后果的详细特征 在这个动物模型中接触可卡因将有助于理解潜在的分子和 扰乱临床人群行为的细胞机制。

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.