Possible implications of the dopamine D3 receptor in schizophrenia and in antipsychotic drug actions
Possible implications of the dopamine D3 receptor in schizophrenia and in antipsychotic drug actions
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DOI：
10.1016/s0165-0173(99)00043-0
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发表时间：
2000-03-01
影响因子：
--
通讯作者：
Sokoloff, P
中科院分区：
文献类型：
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作者：
Schwartz, JC;Diaz, J;Sokoloff, P
D-3受体可能是抗精神病药物的重要靶点，这些药物都以高亲和力结合，并且在重复给药时不会诱导耐受或受体上调。Dg受体位于大脑区域，即丘脑核和大脑皮层，涉及被认为在精神分裂症中显示功能缺陷的神经回路。D-3受体的过度表达，这是帕金森氏病啮齿动物模型中左旋多巴的行为敏化的原因，也可能是精神分裂症中观察到的多巴胺激动剂敏化的原因。D-3受体在大脑发育过程中的外观，早期在增殖的神经上皮细胞和后来在边缘区的神经元，建议进一步研究，以评估其参与精神分裂症的神经发育障碍。最后，对30项包含2500多名患者的类似研究的荟萃分析表明，D-3受体编码序列的多态性与疾病易感性的小但显著增强相关。(C)2000 Elsevier Science B. V.保留所有权利。
The D-3 receptor may represent an important target for antipsychotic drugs which all bind with high affinity and do not induce upon repeated administration either tolerance or receptor upregulation. The Dg receptor is localized in brain areas, namely the nucleus accumbens and cerebral cortex, implicated in neural circuits believed to display defective functioning in schizophrenia. Overexpression of the D-3 receptor, which accounts for the behavioral sensitization to levodopa in a rodent model of Parkinson's disease, might also be responsible for the sensitization to dopamine agonists observed in schizophrenia. The appearance of the D-3 receptor during brain development, early in proliferating neuroepithelia and later in neurons from limbic areas, suggests further studies to assess its participation in the neurodevelopmental disorders of schizophrenia. Finally, meta-analysis of similar to 30 studies comprising over 2500 patients indicate that a polymorphism in the coding sequence of the D-3 receptor is associated with a small but significant enhancement of vulnerability to the disease. (C) 2000 Elsevier Science B.V. All rights reserved.