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Developmental consequences of in utero cocaine

子宫内可卡因的发育后果

基本信息

批准号：
7367130
负责人：
BARBARA L THOMPSON
金额：
$ 5.29万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
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/7367130
关键词：
Acute Adolescent Agonist Animal Model Animals Anterior Area Attention Attention Deficit Disorder Bathing Behavior Behavioral Biological Models Cells Cerebral cortex Child Clinical Clinical Research Cocaine Cognitive Complex Coupling Data Development Developmental Process Disruption Dopamine Dopamine Receptor Dose Employee Strikes Exhibits Fetal Cocaine Exposure Fire - disasters Functional disorder GTP-Binding Protein alpha Subunits Goals Human In Situ Interneurons Label Laboratories Left Localized Medial Mediating Membrane Potentials Modeling Molecular Neurons Norepinephrine Norepinephrine Receptors Numbers Oryctolagus cuniculus Outcome Parvalbumins Pattern Performance Phenotype Physiological Population Prefrontal Cortex Preparation Primates Property Receptor Signaling Research Design Research Personnel Rest Rodent Role Slice Structure System Testing Thinking Tissues behavior change behavioral pharmacology calbindin calretinin cingulate cortex critical developmental period design dopamine system functional outcomes gamma-Aminobutyric Acid in utero monoamine neurophysiology neurotransmission postnatal prenatal programs receptor receptor expression receptor function research study response species difference

项目摘要

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.

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。