PSYCHOTROPIC DRUGS AND SEROTONIN RECEPTORS

这个项目的目的是确定地点和 不同人群推定5-羟色胺的药理敏感性 (5-羟色胺，5-羟色胺)受体在中枢神经系统。 为了实现这一点，该项目被设计为一个跨学科的项目。 利用放射自显影定位技术 配基结合部位与计算机辅助显微密度计量学 图像处理。配体结合技术在脑研究中的应用 匀浆至少鉴定出了两种主要的 可能的5-羟色胺受体，5-羟色胺1和5-羟色胺2受体。在……里面 此外，我们已经证明了5-HT1站点，由 3 H-5-羟色胺的高亲和力结合，实际上代表了一种异质性 网站的数量，现在有数据表明， 5-HT1位点亚型的相关性。结果使用 放射自显影技术表明它可以用来提供一种手段 确定这些地点在非常小的范围内的准确分布 大脑的各个区域。这种本地化是可能的，因为 可区分不同类型药物的可获得性 5-羟色胺受体。例如，抗精神病药螺环酮至少显示出 两个不同种群的亲和力差异3000倍 大鼠脑内的~3H-5-羟色胺结合部位，因此有可能 选择能抑制药物结合的药物浓度 ~3H-5-羟色胺与一个部位结合而不影响其与另一个部位的结合。最近， 我们还确定了其他化合物，如裸盖菇素和其他 吲哚胺，也可以区分不同类型的~3H-5-羟色胺 网站。因此，将放射自显影技术与可以 区分不同类型的5-羟色胺受体应该允许 5-羟色胺能受体亚型在体内的定位 中枢神经系统。因为5-羟色胺与许多行为和 疾病状态，包括睡眠、进食、感觉疼痛、抑郁和 精神分裂症不一而足，希望本土化和 不同类型的5-羟色胺能受体的特征将有助于 确定本中心的角色和相应的行动地点 神经递质和最终导致开发新的治疗方法 探员们。

The purpose of this project is to determine the location and pharmacological sensitivity of different populations of putative serotonin (5-hydroxytryptamine, 5-HT) receptors in the central nervous system (CNS). To accomplish this the project is designed as an interdisciplinary program utilizing the technique for the autoradiographic localization of ligand-binding sites coupled with computer-assisted microdensitometry and image processing. Application of the ligand-binding technique to brain homogenates has resulted in the identification of at least two major populations of putative 5-HT receptors, the 5-HT1 and 5-HT2 receptors. In addition, we have demonstrated that the 5-HT1 sites, defined by the high-affinity binding of 3H-5-HT, actually represent a heterogeneous population of sites, and there are now data suggesting functional correlates of the subtypes of 5-HT1 sites. Results using the autoradiographic technique suggest that it can be used to provide a means of determining the precise distributions of these sites within very small areas of the brain. Such localization is possible because of the availability of drugs which can distinguish between the different types of 5-HT receptors. For example, the neuroleptic spiperone shows at least a 3000-fold difference in its affinities for two different populations of 3H-5-HT binding sites in the rat brain, and it is therefore possible to select a concentration of this drug which can inhibit the binding of 3H-5-HT to one site without affecting its binding to the other. Recently, we have also determined that other compounds, e.g., psilocybin and other indoleamines, can also discriminate between different types of 3H-5-HT sites. Thus, combining the autoradiographic technique with drugs which can discriminate between different types of 5-HT receptors should allow the localization of specific subtypes of putative serotonergic receptors within the CNS. Since serotonin has been implicated in a number of behaviors and disease states, including sleep, eating, perception of pain, depression and schizophrenia to name a few, it is hoped that the localization and characterization of different types of serotonergic receptors will aid in defining the roles and corresponding sites of action of this central neurotransmitter and ultimately lead to the development of new therapeutic agents.