EFFECT OF DRUG ABUSE ON THE PLACENTAL OPIATE SYSTEM

我们的长期目标是了解分子机制。 导致人类对阿片类药物的耐受和成瘾。我们选择了一个人类 器官，胎盘，作为我们研究的模型系统。这个器官提供了 几个优势，如人类起源、可用性、包含 阿片系统的组成部分--即kappa受体及其天然 配体强啡肽1-8--受母亲滥用阿片类药物的影响 怀孕了。此外，人类胎盘小叶可以在体外进行灌流 在母体和胎儿方面进行长达24小时的研究 致畸物质对其生理的影响。 这项提议涉及三个具体目标：第一，确定 Kappa阿片受体及其天然配体的分离纯化 强啡肽1-B来自胎盘绒毛组织。二是要深入研究 胎盘绒毛组织的生理意义。第二，为了 即研究胎盘阿片系统的生理学意义 阿片类药物对乙酰胆碱和绒毛组织LCG释放的调节作用。这个 第三，研究孕期母亲滥用阿片类药物对健康的影响 胎盘阿片系统成分的水平，即向上或向下 调节和生理功能，即乙酰胆碱和LCG的释放。 将使用两种主要方法来获得关于以下各项影响的数据 怀孕期间滥用阿片类药物：第一，通过对 从参加美沙酮治疗计划的母亲那里获得的胎盘 怀孕了。第二，来自用正常胎盘进行的实验 患者，并在体外灌流他们在一个双叶诱导系统中 24小时服用鸦片类药物。从这两种方法获得的数据将 为阿片类药物对胎盘的慢性影响提供证据 生理学。所得出的结论将有助于我们理解这些机制。 人类中的阿片成瘾。

Our long term objectives are the understanding of the molecular mechanisms leading to opioid tolerance and addiction in human. We have chosen a human organ, the placenta, as a model system for our studies. This organ offers several advantages such as human origin, availability, containing components of the opiate system--namely kappa receptors and their natural ligand dynorphin 1-8--which are affected by maternal opiate abuse during pregnancy. In addition, the human placental lobule can be perfused in vitro for up to 24 hours on the maternal and fetal side allowing studies on the effects of tertogens on its physiology. This proposal addresses three specific aims: the first, to characterize the isolated and purified kappa opiate receptor and its natural ligand dynorphin 1-B from placental villus tissue. The second, to study the physiologic significance of the placental villus tissue. The second, to study the physiologic significance of the placental opiate system namely opioid modulation of acetylcholine and LCG release from villus tissue. The third, to study the effects of maternal opioid abuse during pregnancy on the levels of the placental opiate system components i.e. up or down regulation and physiologic function i.e. acetylcholine and LCG release. Two main approaches will be used to obtain the data on the effects of opiate abuse during pregnancy: the first, by conducting experiments on placenta obtained from mothers in methadone treatment programs during pregnancy. The second, from experiments using placenta obtained from normal patients and perfusing them in vitro in a dual lobule persusion system with opiates for 24 hours. The data obtained from the two approaches will provide evidence for the chronic effects of opiates on placental physiology. The conclusions drawn will help us understand the mechanisms of opiate addiction in human.