AUTORADIOGRAPHIC MAPPING OF OPIATE RECEPTORS

内源性阿片系统具有几种功能，以及 是鸦片类药物的目标，对鸦片上瘾是主要的 社会问题。尽管关于这个系统的重要信息 在人类大脑中是稀有的。因此，我们建议详细研究 Mu、Delta和Kappa阿片受体的神经解剖学分布 在至少30个大脑中，15个自杀者和15个性别和年龄匹配的对照组。 这两个群体都将涵盖较大的年龄跨度(13至87岁)以及 男女都有足够的代表性。所有的大脑都将是毒品和 神经病理学免费。阿片类药物的神经解剖学分布 结合部位将通过体外定量放射自显影进行研究。 [~3H]DAGO、[~3H]DSLET和[~3H]U69593配体将被用于 分别标记Mu、Delta和Kappa结合位点。广泛性 将对在几个鸡冠台获得的冠状断面进行测绘- 尾侧水平，以便充分代表新皮质、边缘 系统结构，丘脑，基底节和脑干 包括在内。绘制的地点的特征，根据它们的 解离常数(Kd)、最大结合容量(Bmax)和 药理特性将通过饱和和 位移实验。这些都将在膜上进行 取自同一大脑的前额叶皮质样本的制备。大小 这个大脑样本的人口统计组成将使我们能够 提供关于阿片类药物分布的定量规范信息 人脑中的结合部位。此信息对以下方面有价值 了解内源性阿片系统在疼痛中的作用 知觉和食欲行为以及各种病理 涉及鸦片系统的条件。年龄和年龄的影响 阿片类药物结合部位的性行为可以从我们的样本和帮助中推断出来 了解这些因素在各种行为中所起的作用 在鸦片系统的帮助下。两个分布之间的比较 从自杀受害者的大脑中提取并适当匹配 控制将有助于理解阿片系统在 自杀行为和可能的抑郁症。数据将使用以下工具进行分析 多变量技术。除了对年龄、性别的描述 自杀效应以及它们之间的相互作用，分布 阿片结合位点的分布将与阿片类药物的分布相关 甘露能系统的标志物来自相同的大脑。这 后一种分析将促进对相互关系的理解 在人脑中不同的神经体液系统之间。

The endogenous opiate system subserves several functions, as well as being the target of opium-like drugs, the addiction to which is a major social problem. Albeit it's importance information concerning this system in the human brain is scarce. Therefore we propose to study in detail the neuroanatomical distribution of the mu, delta, and kappa opiate receptors in, at least, 30 brains, 15 suicides and 15 sex and age matched controls. Both group will cover a large age span (13 to 87 years) as well as adequate representation of both sexes. All brains will be drug and neuropathology free. The neuroanatomical distribution of the opioid binding sites will be studied by in vitro quantitative autoradiography. Triatiated ligands, [3H] DAGO, [3H]DSLET and [3h]U69593, will be used to label the mu, delta and kappa binding sites, respectively. Extensive mapping will be performed on coronal sections obtained at several rostro- caudal levels, so that adequate representation of neocortex, limbic system structures, thalamus, basal ganglia and brain stem will be included. Characterization of the mapped sites, in terms of their dissociation constant (Kd), maximal binding capacity (Bmax), and pharmacological properties will be carried out through saturation and displacement experiments. These will be performed on membrane preparations of prefrontal cortex samples from the same brains. The size and demographic composition of this sample of brains will enable us to provide quantitative normative information on the distribution of opioid binding sites in the human brain. This information is valuable for understanding the involvement of the endogenous opiate system in pain perception and appetitive behavior as well as a variety of pathological conditions in which the opiate system is involved. The effects of age and sex on opioid binding sites can be deduced from our sample and help understand the role played by these factors in a variety of behaviors subserved by the opiate system. Comparison between the distributions obtained from brains of suicide victims and appropriately matched controls will help to understand the role of the opiate system in suicidal behavior and possibly depression. Data will be analyzed using multivariate techniques. In addition to the characterization of age, sex and suicide effects and the interactions between them, the distribution of opioid binding sites will be correlated with the distributions of markers of manoaminergic systems derived from the same brains. This latter analysis will promote the understanding of interrelationships between different neurohumoral systems in the human brain.