Bannon M J, Roth R H
Pharmacol Rev. 1983 Mar;35(1):53-68.
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.
目前有关多巴胺（DA）对前额叶皮质神经支配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综合。中脑皮质DA系统的一些可能功能，是从对前额叶皮质在行为中的作用所进行的广泛研究中提出的，同时也来自于有关前额叶皮质对皮质下DA系统输出进行调节的数据。与此同时，对中脑皮质DA神经元的解剖学、行为学、生物化学和电生理学研究，很大程度上源于人们对确定各种精神药物，特别是抗精神病药物（DA拮抗剂）的作用位点和作用机制的兴趣。一个相关的研究领域探讨了DA自身受体的功能作用。与黑质纹状体/中脑边缘DA系统相比，中脑皮质DA系统具有许多独特的特征，包括：1）较高的DA更新率；2）较高的神经元放电率和不同的放电模式；3）对DA激动剂和拮抗剂的反应性大大降低；4）对长期给予的DA拮抗剂的作用缺乏耐受性；5）对足底电击应激有选择性激活。这些特征可能是由于投射到前额叶皮质的DA细胞缺乏DA自身受体，而DA自身受体是皮质下DA系统生理和药理调节的重要位点。最近对分别支配前扣带回和梨状皮质的两个不同DA系统的研究进一步支持了这一观点：前一个系统缺乏DA自身受体，其反应与前额叶皮质DA系统非常相似；后一个系统具有功能性DA自身受体，表现出与黑质纹状体/中脑边缘DA系统相似的药理反应性（11、14、118、119、38）。自身受体可能是未来合理药物设计的一个重要靶点。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，如果这些药物在精神分裂症患者中被证明无效，这可能有助于解释迄今为止用低剂量（自身受体特异性）、选择性较低的DA激动剂治疗精神分裂症所得到的模棱两可的结果（综述见参考文献97）。DA自身受体激动剂缺乏临床疗效也可能表明，如果一个DA系统间接参与精神分裂症，那么抗精神病药物的治疗作用位点是一个缺乏自身受体的DA系统（如支配前额叶皮质的DA系统）。
