Heinz A
Zentralinstitut für Seelische Gesundheit, Mannheim.
Nervenarzt. 2000 Jan;71(1):54-7. doi: 10.1007/s001150050008.
The dopamine hypothesis of schizophrenia was based on the neuroleptical blockade of central dopamine D2 receptors. Brain imaging studies, however, generally failed to demonstrate a significant increase in central D2 receptors among schizophrenic patients. Using a novel approach, the group of Laruelle and Abi-Dargham was now able to demonstrate that schizophrenic patients have increased synaptic dopamine concentrations in the striatum. Endogenous dopamine competes with a radioligand for binding at dopamine D2 receptors; compared to healthy control subjects, blockade of dopamine production in neuroleptic-naive schizophrenic patients induced a significantly higher increase in D2 binding of the infused radioligand, indicating higher endogenous synaptic dopamine. A similar increase in D2 binding was also observed in drug-free schizophrenics who had previously been treated with neuroleptics; these patients also showed an increased density of striatal D2 receptors, most likely due to counteradaptive upregulation of D2 receptors during neuroleptic medication. The Columbia study provides an important indication of hyperdopaminergic function in schizophrenia.
精神分裂症的多巴胺假说基于中枢多巴胺D2受体的抗精神病药物阻断作用。然而，脑成像研究通常未能证明精神分裂症患者中枢D2受体有显著增加。使用一种新方法，拉鲁埃尔和阿比-达格姆团队现在能够证明，精神分裂症患者纹状体中的突触多巴胺浓度增加。内源性多巴胺与放射性配体竞争结合多巴胺D2受体；与健康对照受试者相比，未服用过抗精神病药物的精神分裂症患者多巴胺生成被阻断后，注入的放射性配体的D2结合显著增加，表明内源性突触多巴胺水平更高。在之前接受过抗精神病药物治疗的未服药精神分裂症患者中也观察到类似的D2结合增加；这些患者还表现出纹状体D2受体密度增加，这很可能是由于抗精神病药物治疗期间D2受体的适应性上调。哥伦比亚大学的这项研究为精神分裂症中多巴胺能功能亢进提供了重要证据。
