EFFECT OF DRUG ABUSE ON THE PLACENTAL OPIATE SYSTEM

我们的长期目标是了解分子机制 从而导致人的阿片耐受和成瘾。我们选择了一个人类 器官，胎盘，作为我们研究的模型系统。该机构提供 几个优点，如人类起源，可用性，包含 阿片系统的组成部分-即κ受体及其天然的 强啡肽配体1-8-这是受母体阿片类药物滥用的影响， 怀孕此外，人胎盘小叶可进行体外灌注 在母体和胎儿侧长达24小时， 对植物生理的影响。 这项建议涉及三个具体目标：第一， 分离和纯化的κ阿片受体及其天然配体 胎盘绒毛组织中强啡肽1-B。第二，研究 胎盘绒毛组织的生理意义。另一个前往 研究胎盘阿片系统的生理意义，即 绒毛组织中乙酰胆碱和LCG释放的阿片调节。的 第三，研究母亲在怀孕期间滥用阿片类药物对 胎盘阿片系统成分的水平，即上升或下降 调节和生理功能，即乙酰胆碱和LCG释放。 将采用两种主要方法来获得关于 怀孕期间滥用阿片类药物：第一，通过对 从美沙酮治疗计划中的母亲身上获得的胎盘 怀孕第二，来自使用正常人胎盘的实验， 患者，并在体外将其灌注在双叶诱导系统中， 鸦片24小时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了证据 physiology.所得出的结论将有助于我们了解 人类的鸦片成瘾

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.