Increased baseline occupancy of D2 receptors by dopamine in schizophrenia
Increased baseline occupancy of D2 receptors by dopamine in schizophrenia
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DOI：
10.1073/pnas.97.14.8104
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发表时间：
2000-07-05
影响因子：
11.1
通讯作者：
Laruelle, M
中科院分区：
文献类型：
--
作者：
Abi-Dargham, A;Rodenhiser, J;Laruelle, M
精神分裂症的经典多巴胺假说假定在D - 2受体处存在多巴胺能传递亢进。我们通过比较药理学诱导的急性多巴胺耗竭前后D - 2受体的可利用性，测量了18例未经治疗的精神分裂症患者和18例匹配的对照者体内多巴胺对纹状体D - 2受体的占有率。与对照受试者（9%±7%，P = 0.003）相比，精神分裂症患者突触内多巴胺的急性耗竭导致D - 2受体可利用性增加幅度更大（19%±11%）。多巴胺对D - 2受体占有率的增加既出现在首次发病且未使用过抗精神病药物的患者中，也出现在先前接受过治疗且病情加重发作的慢性患者中。此外，突触多巴胺升高可预测阳性症状对抗精神病药物的良好治疗反应。这一发现提供了精神分裂症中多巴胺对D - 2受体刺激增加的直接证据，与多巴胺能神经元的阶段性活动增加相一致。
The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D-2 receptor. We measured in vivo occupancy of striatal D-2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D-2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D-2 receptor availability in patients with schizophrenia (19% +/- 11%) compared with control subjects (9% +/- 7%, P = 0.003). The increased occupancy of D-2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D-2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.