Department of Neurology, University of Debrecen, H-4012 Debrecen, Hungary.
Brain Res Bull. 2012 Apr 10;87(6):504-10. doi: 10.1016/j.brainresbull.2012.02.012. Epub 2012 Mar 7.
Cannabinoid type-1 receptors (CB₁Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB₁Rs play an important role in the regulation of motor activities in the striatum. In the present study, we used human brain samples to examine the relationship between CB₁R and dopamine receptor density in case of Parkinson's disease (PD). Post mortem putamen, nucleus caudatus and medial frontal gyrus samples obtained from PD patients were used for CB₁R and dopamine D₂/D₃ receptor autoradiography. [¹²⁵I]SD7015, a novel selective CB₁R inverse agonist, developed by a number of the present co-authors, and [³H]raclopride, a dopamine D₂/D₃ antagonist, were used as radioligands. Our results demonstrate unchanged CB₁R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (L-DOPA). At the same time dopamine D₂/D₃ receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 ± 10.00 fmol/g, PD: 3.73 ± 0.07 fmol/g (mean ± SEM), p<0.05) and nucleus caudatus (control: 30.26 ± 2.48 fmol/g, PD: 12.84 ± 5.49 fmol/g, p<0.0005) samples. In contrast to the putamen and the nucleus caudatus, in the medial frontal gyrus neither receptor densities were affected. Our data suggest the presence of an unaltered CB₁R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB₁R population which, in line with the conclusion of earlier publications, may be utilized as a pharmacological target in the treatment of PD. Furthermore we found discrepancy between a maintained CB₁R population and a decreased dopamine D₂/D₃ receptor population in PD striatum. The precise explanation of this conundrum requires further studies with simultaneous examination of the central cannabinoid and dopaminergic systems in PD using higher sample size.
大麻素 1 型受体（CB1R）通过参与成年大脑中的逆行信号转导来调节突触神经传递。越来越多的证据表明，大麻素通过 CB1R 在纹状体运动活动的调节中发挥重要作用。在本研究中，我们使用人脑样本检查了帕金森病（PD）患者中 CB1R 和多巴胺受体密度之间的关系。从 PD 患者中获得死后纹状体、尾状核和内侧额回样本，用于 CB1R 和多巴胺 D2/D3 受体放射自显影。[¹²⁵I]SD7015 是由本研究的多位共同作者开发的新型选择性 CB1R 反向激动剂，[³H]raclopride 是一种多巴胺 D2/D3 拮抗剂，用作放射性配体。我们的结果表明，接受左旋多巴（L-DOPA）治疗的已故 PD 患者的纹状体和尾状核 CB1R 密度不变。同时，PD 纹状体多巴胺 D2/D3 受体的密度水平显著降低（对照组：47.97±10.00 fmol/g，PD：3.73±0.07 fmol/g（均值±SEM），p<0.05）和尾状核（对照组：30.26±2.48 fmol/g，PD：12.84±5.49 fmol/g，p<0.0005）样本。与纹状体和尾状核相反，在内侧额回中，两种受体的密度均不受影响。我们的数据表明，即使在接受左旋多巴治疗的 PD 晚期，也存在未改变的 CB1R 群体。这进一步支持了完整的 CB1R 群体的存在，这与早期出版物的结论一致，可能被用作 PD 治疗的药理学靶点。此外，我们发现在 PD 纹状体中，CB1R 群体保持不变，而多巴胺 D2/D3 受体群体减少。要准确解释这个难题，需要进一步研究，使用更大的样本量同时检查 PD 中中枢大麻素和多巴胺能系统。
