Meissner Wassilios, Harnack Daniel, Hoessle Nora, Bezard Erwan, Winter Christine, Morgenstern Rudolf, Kupsch Andreas
Department of Neurology, Charité Campus Virchow, Humboldt-University Berlin, Berlin, Germany.
Neurochem Int. 2004 Mar;44(4):281-6. doi: 10.1016/s0197-0186(03)00138-4.
High frequency stimulation (HFS) of the subthalamic nucleus (STN) is thought to be superior to stimulation of the internal pallidum (GPi) in alleviating symptoms of Parkinson's disease (PD). However, preliminary controlled studies comparing the effectiveness of both targets have not found significant differences in the improvement of parkinsonian symptoms, but have shown that STN stimulation allows a dramatic decrease in dopaminergic medication. We have previously shown that STN-HFS increases striatal extracellular dopamine (DA) metabolites, but not DA, in both naive and 6-hydroxydopamine (6-OHDA)-lesioned rats, whereas stimulation of the entopeduncular nucleus (EP), the rodent equivalent of the internal pallidum, does not affect DA or metabolite levels. Intriguingly, STN-HFS increases striatal DA release after inhibition of DA reuptake or metabolism, suggesting that this observation may have been obscured in non-drug treated animals by rapid and effective DA reuptake. Since STN-HFS further enhances DA metabolism after DA reuptake inhibition or depletion it has been proposed that STN-HFS increases both, striatal DA release and metabolism, independently. Therefore, the present study assesses the impact of EP-HFS on striatal DA release and metabolism in normal rats after inhibition of DA reuptake or metabolism, using microdialysis. In summary, our data demonstrate that, contrary to STN stimulation, EP-HFS has no effect on striatal DA release and metabolism. Thus, the present study provides a partial explanation for the reported clinical differences, and experimental evidence for differential mechanisms of action between HFS of the internal pallidum and the STN, that are most likely related to differences in functional anatomy.
丘脑底核（STN）的高频刺激（HFS）在缓解帕金森病（PD）症状方面被认为优于苍白球内侧部（GPi）刺激。然而，比较这两个靶点有效性的初步对照研究并未发现帕金森病症状改善方面的显著差异，但显示STN刺激可使多巴胺能药物用量大幅减少。我们之前已经表明，在未处理和6-羟基多巴胺（6-OHDA）损伤的大鼠中，STN-HFS均可增加纹状体细胞外多巴胺（DA）代谢产物，但不增加DA，而刺激内苍白球的啮齿类动物等效物——脚内核（EP），则不影响DA或代谢产物水平。有趣的是，在抑制DA再摄取或代谢后，STN-HFS会增加纹状体DA释放，这表明在未用药物处理的动物中，这一现象可能因快速有效的DA再摄取而被掩盖。由于在抑制DA再摄取或耗竭后，STN-HFS会进一步增强DA代谢，因此有人提出，STN-HFS可独立增加纹状体DA释放和代谢。因此，本研究使用微透析评估了在抑制DA再摄取或代谢后，EP-HFS对正常大鼠纹状体DA释放和代谢的影响。总之，我们的数据表明，与STN刺激相反，EP-HFS对纹状体DA释放和代谢没有影响。因此，本研究为所报道的临床差异提供了部分解释，并为苍白球内侧部和STN的高频刺激之间不同的作用机制提供了实验证据，这很可能与功能解剖学差异有关。
