Department of Nuclear Medicine, University of Mainz, Mainz, Germany.
Epilepsia. 2010 Mar;51(3):415-22. doi: 10.1111/j.1528-1167.2009.02272.x. Epub 2009 Aug 19.
Alterations in dopamine neurotransmission in animal models of epilepsies have been frequently demonstrated using invasive neuroscience or ex vivo techniques. We aimed to test whether corresponding alterations could be detected by noninvasive in vivo brain imaging with positron emission tomography (PET) in the chronic phase of the rat pilocarpine model of temporal lobe epilepsy.
Six pilocarpine-treated Wistar rats exhibiting spontaneous recurrent seizures and nine control rats were studied with PET using [(18)F]-fallypride, a high-affinity dopamine D(2/3) receptor ligand. Parametric images of [(18)F]-fallypride specific binding were calculated using a reference tissue method, and the two groups were contrasted by whole-brain voxel-based analysis implemented in statistical parametric mapping (SPM5).
Dopamine D(2/3) receptor availability was 27% lower in the bilateral anterior caudate-putamen of pilocarpine-treated rats as compared to controls (p < 0.05), but binding was unaffected in other striatal or extrastriatal regions.
The finding of substantially reduced availability of dopamine D(2/3) receptors in the anterior caudate-putamen of rats during the chronic phase of the pilocarpine model is in agreement with results of invasive (microinjection, microdialysis) animal studies that have revealed increased dopamine tonus and a D(2/3) receptor-mediated anticonvulsant action of dopamine in the anterior segment of the rat striatum. The present PET approach could be prospectively applied for monitoring dopamine receptor changes longitudinally, that is, at different phases of the epileptogenic process, and opens perspectives for testing dopaminergic agents as potential antiepileptogenic drugs.
在癫痫动物模型中，已经通过侵袭性神经科学或离体技术频繁证明多巴胺神经传递的改变。我们旨在通过正电子发射断层扫描（PET）在颞叶癫痫大鼠匹鲁卡品模型的慢性期进行非侵入性体内脑成像，以测试是否可以检测到相应的改变。
使用 [(18)F]-fallypride（一种高亲和力的多巴胺 D2/3 受体配体）对 6 只表现出自发性复发性发作的匹鲁卡品处理的 Wistar 大鼠和 9 只对照大鼠进行 PET 研究。使用参考组织方法计算 [(18)F]-fallypride 特异性结合的参数图像，然后通过统计参数映射（SPM5）中的全脑体素基于分析对两组进行对比。
与对照组相比，匹鲁卡品处理大鼠双侧前尾状核-壳核中的多巴胺 D2/3 受体可用性降低了 27%（p < 0.05），但在其他纹状体或纹状体外区域，结合不受影响。
在匹鲁卡品模型的慢性期，大鼠前尾状核-壳核中多巴胺 D2/3 受体的可用性显著降低的发现与侵袭性（微注射，微透析）动物研究的结果一致，这些研究表明在大鼠纹状体的前节中，多巴胺张力增加和多巴胺 D2/3 受体介导的抗惊厥作用。目前的 PET 方法可以前瞻性地应用于纵向监测多巴胺受体的变化，即癫痫发生过程的不同阶段，并为测试多巴胺能药物作为潜在的抗癫痫药物开辟了前景。
