Pharmacology of mesocortical dopamine neurons.
Pharmacology of mesocortical dopamine neurons.
复制标题
DOI：
--
复制
发表时间：
1983-03
影响因子：
21.1
通讯作者：
M. Bannon;R. Roth
中科院分区：
文献类型：
--
作者：
M. Bannon;R. Roth
目前关于DA神经支配前额皮质的药理学和功能的信息是来自几个最初不同研究领域的数据的综合。大量关于前额叶皮层在行为中的作用的研究，以及前额叶皮层对皮层下数据处理系统输出的调节数据，提出了中皮层数据处理系统可能具有的一些功能。同时，对中皮质DA神经元的解剖学、行为学、生化和电生理学的研究在很大程度上源于对确定各种精神药物，特别是抗精神病药物（DA拮抗剂）的作用部位和机制的兴趣。一个相关的研究领域已经研究了DA自受体的功能作用。与黑质纹状体/中边缘DA系统相比，中脑皮层DA系统具有许多独特的特征，包括1)更高的DA周转率，2)更高的神经元放电率和不同的模式，3)对DA激动剂和拮抗剂的反应性大大降低，4)对长期服用DA拮抗剂的作用缺乏耐受性，5)足震应激的选择性激活。这些特征可能是由于投射到前额叶皮层的DA细胞缺乏DA自受体，而DA自受体是皮层下DA系统生理和药理调节的重要部位。最近对分别支配前扣带皮层和梨状皮质的两种不同的DA系统的研究进一步支持了这一论点：前者缺乏DA自身感受器，其反应与前额皮质DA系统非常相似；后一系统具有功能性DA自受体，表现出与黑质纹状体/中边缘DA系统相似的药理学反应（11,14,118,119,38）。自体受体可能是未来合理药物设计的重要靶点。例如，对DA自身受体更具选择性的DA激动剂（65,72）可能是治疗精神分裂症的有用药物。然而，如果这些药物被证明对精神分裂症患者无效，它可能有助于解释迄今为止在使用低剂量（自受体特异性）低选择性DA激动剂治疗精神分裂症时获得的模棱两可的结果（回顾，见参考文献97）。DA自身受体激动剂缺乏临床疗效也可能表明，如果DA系统间接参与精神分裂症，抗精神病药物的治疗作用部位是缺乏自身受体的DA系统（如支配前额叶皮层的DA系统）。
The current information on the pharmacology and function of the DA innervation to the prefrontal cortex is a synthesis of data from several initially distinct areas of research. Some possible functions of the mesocortical DA system are suggested from the extensive studies conducted on the role of the prefrontal cortex in behavior, and also from the data on prefrontal cortical modulation of the output of subcortical DA systems. Meanwhile, anatomical, behavioral, biochemical, and electrophysiological studies on mesocortical DA neurons have largely resulted from interest in determining the site(s) and mechanism(s) of action of various psychotropic drugs, and particularly the antipsychotic drugs (DA antagonists). An interrelated field of study has investigated the functional role of DA autoreceptors. The mesocortical DA system possesses many unique characteristics compared to the nigrostriatal/mesolimbic DA systems, including 1) a higher DA turnover rate, 2) a higher rate and different pattern of neuronal discharge, 3) a greatly diminished responsiveness to DA agonists and antagonists, 4) a lack of tolerance to the effect of chronically administered DA antagonists, and 5) a selective activation by footshock stress. These characteristics may be due to the fact that the DA cells projecting to the prefrontal cortex lack DA autoreceptors, an important site for the physiological and pharmacological modulation of subcortical DA systems. This contention is further supported by recent studies on two distinct DA systems innervating, respectively, the anterior cingulate and piriform cortices: the former system, which lacks DA autoreceptors, responds much like the prefrontal cortical DA sy stem; the latter system, which possesses functional DA autoreceptors, manifests a pharmacological responsiveness similar to the nigrostriatal/mesolimbic DA systems (11, 14, 118, 119, 38). Autoreceptors may be an important target for future rational drug design. For example, DA agonists more selective for DA autoreceptors (65, 72) may be useful agents in the treatment of schizophrenia. If, however, these drugs prove ineffective in schizophrenic patients, it might help to explain the equivocal results obtained to date in the treatment of schizophrenia with low (autoreceptor-specific) doses of less selective DA agonists (for a review, see Ref. 97). A lack of clinical efficacy of DA autoreceptor agonists might also suggest that if a DA system is indirectly involved in schizophrenia the site of therapeutic action of antipsychotic drugs is a DA system (such as that innervating the prefrontal cortex) that lacks autoreceptors.