Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, USA.
CNS Neurosci Ther. 2011 Apr;17(2):104-9. doi: 10.1111/j.1755-5949.2010.00230.x. Epub 2010 Dec 27.
Presynaptic dopamine (DA) transmission has been measured in schizophrenia using different paradigms aimed at providing estimates of the integrity or the activity of the presynaptic dopaminergic neuron. RESEARCHERS HAVE MEASURED: (1) DA synthesis capacity with [(18) F]DOPA, a measure of the activity of dopa decarboxylase, (2) DA release with studies measuring the impact of a DA releasing stimulant challenge on the binding of a D(2) receptor radiotracer, (3) D(2) baseline occupancy by DA, a measure of baseline intrasynaptic DA, assessed by the changes in binding of D(2) radiotracer induced by DA depletion, and (4) the DA and the vesicular monoamine transporters, to assess the integrity of presynaptic terminals. The relationship between DA release and D(2) receptor occupancy at baseline by DA has also been assessed in the same patients. Overall, these different imaging modalities have converged to show a dysregulation of presynaptic dopaminergic activity in schizophrenia, leading to excessive DA release in the striatum, particularly in the projection to the associative striatum, an area of integration between cognitive and limbic cortical inputs. Excessive striatal presynaptic DA is linked to the emergence of acute psychotic symptoms and to their response to treatment in schizophrenia. Understanding the etiology of this dysregulation and its consequences on the rest of the circuitry is important for future drug development.
（1）使用 [(18) F]DOPA 测量多巴胺（DA）合成能力，这是多巴脱羧酶活性的衡量标准，（2）通过测量多巴胺释放刺激物对 D2 受体放射性示踪剂结合的影响来测量 DA 释放，（3）DA 通过 DA 耗竭引起的 D2 放射性示踪剂结合变化来评估基线突触内 DA 的 D2 基线占用，（4）DA 和囊泡单胺转运体，以评估突触前末端的完整性。还在同一批患者中评估了 DA 释放与 DA 对基线 D2 受体占有率之间的关系。总体而言，这些不同的成像方式已经趋于一致，表明精神分裂症中存在突触前多巴胺能活动失调，导致纹状体中 DA 释放过度，特别是在与认知和边缘皮质输入整合的关联纹状体的投射中。纹状体中过度的突触前 DA 与急性精神病症状的出现及其对精神分裂症治疗的反应有关。了解这种失调的病因及其对其他电路的影响对于未来的药物开发非常重要。
