Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects
Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects
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DOI：
10.1073/pnas.93.17.9235
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发表时间：
1996-08-20
影响因子：
11.1
通讯作者：
Innis, RB
中科院分区：
文献类型：
--
作者：
Laruelle, M;Abi-Dargham, A;Innis, RB
精神分裂症的多巴胺假说提出，多巴胺能传递的亢进与这种疾病有关，但对精神分裂症中多巴胺功能异常的直接观察一直难以实现。我们使用一种新开发的单光子发射计算机断层扫描方法，测量了15名精神分裂症患者和15名健康对照者纹状体中安非他明诱导的多巴胺释放。安非他明诱导的多巴胺释放通过安非他明诱导的多巴胺D - 2受体可利用性的降低来评估，以特异性D - 2受体放射性示踪剂[I - 123](S)-(-)-3 - 碘 - 2 - 羟基 - 6 - 甲氧基 - N - [(1 - 乙基 - 2 - 吡咯烷基)甲基]苯甲酰胺([I - 123]IBZM)的结合电位来衡量。与对照组（-7.6±2.1%）相比，精神分裂症组中安非他明诱导的[I - 123]IBZM结合电位的降低明显更大（-19.5±4.1%）。在精神分裂症组中，安非他明对[I - 123]IBZM结合电位的增强作用与阳性精神病性症状的出现或恶化有关。这一结果表明，在这种实验环境下精神分裂症患者出现的精神病性症状与多巴胺能传递的过度刺激有关。这样的观察结果与精神分裂症中多巴胺能神经元的异常反应性是相符的。
The dopamine hypothesis of schizophrenia proposes that hyperactivity of dopaminergic transmission is associated with this illness, but direct observation of abnormalities of dopamine function in schizophrenia has remained elusive, We used a newly developed single photon emission computerized tomography method to measure amphetamine-induced dopamine release in the striatum of fifteen patients with schizophrenia and fifteen healthy controls, Amphetamine-induced dopamine release was estimated by the amphetamine-induced reduction in dopamine D-2 receptor availability, measured as the binding potential of the specific D-2 receptor radiotracer [I-123] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([I-123]IBZM), The amphetamine-induced decrease in [I-123]IBZM binding potential was significantly greater in the schizophrenic group (-19.5 +/- 4.1%) compared with the control group (-7.6 +/- 2.1%), In the schizophrenic group, elevated amphetamine effect on [I-123]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms, This result suggests that psychotic symptoms elicited in this experimental setting in schizophrenic patients are associated with exaggerated stimulation of dopaminergic transmission. Such an observation would be compatible with an abnormal responsiveness of dopaminergic neurons in schizophrenia.