Laruelle M, Abi-Dargham A, van Dyck C H, Gil R, D'Souza C D, Erdos J, McCance E, Rosenblatt W, Fingado C, Zoghbi S S, Baldwin R M, Seibyl J P, Krystal J H, Charney D S, Innis R B
Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06520, USA.
Proc Natl Acad Sci U S A. 1996 Aug 20;93(17):9235-40. doi: 10.1073/pnas.93.17.9235.
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 D2 receptor availability, measured as the binding potential of the specific D2 receptor radiotracer [123I] (S)-(-)-3-iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl]benzamide ([123I]IBZM). The amphetamine-induced decrease in [123I]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 [123I]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.
精神分裂症的多巴胺假说提出，多巴胺能传递亢进与该疾病相关，但直接观察精神分裂症中多巴胺功能异常仍难以实现。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例精神分裂症患者和15名健康对照者纹状体中苯丙胺诱导的多巴胺释放。通过苯丙胺诱导的多巴胺D2受体可用性降低来估计苯丙胺诱导的多巴胺释放，以特定D2受体放射性示踪剂[123I]（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（[123I]IBZM）的结合潜能来衡量。与对照组（-7.6±2.1%）相比，精神分裂症组中苯丙胺诱导的[123I]IBZM结合潜能降低幅度显著更大（-19.5±4.1%）。在精神分裂症组中，苯丙胺对[123I]IBZM结合潜能的增强作用与阳性精神病性症状的出现或加重相关。这一结果表明，在精神分裂症患者的这种实验环境中引发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相符。
