Jenner P, Marsden C D
University Department of Neurology Institute of Psychiatry, London, England.
Neuropharmacology. 1987 Jul;26(7B):931-40. doi: 10.1016/0028-3908(87)90072-4.
Dopamine receptors in the brain play an important role in the treatment of schizophrenia and in the development of tardive dyskinesia. In Parkinson's disease the loss of dopamine innervation and the use of chronic administration of L-DOPA or therapy with dopamine agonists also affects the function of dopamine receptors in brain. Subacute administration of neuroleptic drugs to rodents for a few weeks followed by the withdrawal of the drug induces supersensitivity of dopamine receptors in the striatum. However, the long-term administration of neuroleptic drugs to rodents shows that typical neuroleptic drugs can induce functional supersensitivity of dopamine receptors despite continued administration of drug. In contrast, atypical neuroleptics such as sulpiride, do not appear to induce the same changes in the activity of dopamine receptors. The functional supersensitivity of dopamine receptors produced by repeated administration of neuroleptic is reflected in changes in cholinergic, gamma-aminobutyric acid (GABA), 5-hydroxytryptamine (5-HT) and peptide neuronal systems. Chronic treatment of parkinsonian patients with drugs may obscure the changes in the function of dopamine receptors caused by the disease process. However, chronic administration of L-DOPA to normal rats and to rats with a unilateral lesions of the nigrostriatal pathway induced with 6-hydroxydopamine does not produce a down-regulation of the number of dopamine receptors. Rather, these experiments indicate the development of a functional supersensitivity of dopamine receptors in the absence of any obvious change in the nature of dopamine receptor populations in brain. In conclusion, while pharmacological manipulation, using neuroleptic drugs, produces the expected development of receptor supersensitivity, studies involving chronic treatment with agonists suggests that dopamine receptors do not always respond as would be predicted. It appears that there are aspects of the regulation of dopamine receptors in brain following pharmacological manipulation which remain to be resolved.
大脑中的多巴胺受体在精神分裂症的治疗以及迟发性运动障碍的发生中起着重要作用。在帕金森病中，多巴胺神经支配的丧失以及长期使用左旋多巴或多巴胺激动剂进行治疗也会影响大脑中多巴胺受体的功能。给啮齿动物亚急性给予抗精神病药物数周，然后停药，会诱导纹状体中多巴胺受体的超敏反应。然而，给啮齿动物长期给予抗精神病药物表明，典型的抗精神病药物尽管持续给药，仍可诱导多巴胺受体的功能性超敏反应。相比之下，非典型抗精神病药物如舒必利似乎不会引起多巴胺受体活性的相同变化。反复给予抗精神病药物所产生的多巴胺受体功能性超敏反应反映在胆碱能、γ-氨基丁酸（GABA）、5-羟色胺（5-HT）和肽能神经元系统的变化中。用药物对帕金森病患者进行长期治疗可能会掩盖疾病过程引起的多巴胺受体功能变化。然而，给正常大鼠和用6-羟基多巴胺诱导黑质纹状体通路单侧损伤的大鼠长期给予左旋多巴，并不会导致多巴胺受体数量的下调。相反，这些实验表明，在大脑中多巴胺受体群体的性质没有任何明显变化的情况下，多巴胺受体出现了功能性超敏反应。总之，虽然使用抗精神病药物进行药理操作会产生预期的受体超敏反应，但涉及激动剂长期治疗的研究表明，多巴胺受体并不总是如预期那样做出反应。看来，药理操作后大脑中多巴胺受体的调节方面仍有待解决。
