The decrease of dopamine D<sub>2sub>/D<sub>3sub> receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB<sub>1sub> cannabinoid receptors in Parkinson's disease: A preliminary autoradiographic study with the

详细信息	查看全文 | 推荐本文 |

• 作者：Szabolcs Farkas<sup>asup> ; Katalin Nagy<sup>asup> ; Zhisheng Jia<sup>bsup> ; Tibor Harkany<sup>csup> ; Mikló ; s Palkovits<sup>dsup> ; Sean R. Donohou<sup>esup> ; Victor W. Pike<sup>esup> ; Christer Halldin<sup>bsup> ; Domokos M&#225 ; thé ; <sup>fsup><sup> ; sup><sup>gsup> ; L&#225 ; szló ; Csiba<sup>asup><sup> ; sup><sup>1sup> ; Bal&#225 ; zs Guly&#225 ; s<sup>bsup><sup> ; sup><sup>1sup><sup> ; sup><sup>balazs.gulyas@ki.sesup>
• 关键词：Parkinson's disease ; Endocannabinoid CB1 receptor ; Dopamine D2/D3 receptor ; Molecular imaging biomarker ; Human brain autoradiography ; Striatum
• 刊名：Brain Research Bulletin
• 出版年：2012
• 期刊代码：9_03619230
• 类别：neu
• 出版时间：10 April, 2012
• 卷：87
• 期：6
• 页码：504-510
• 文件大小：744 K

摘要

Cannabinoid type-1 receptors (CB<sub>1sub>Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB<sub>1sub>Rs 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 CB<sub>1sub>R 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 CB<sub>1sub>R and dopamine D<sub>2sub>/D<sub>3sub> receptor autoradiography. [<sup>125sup>I]SD7015, a novel selective CB<sub>1sub>R inverse agonist, developed by a number of the present co-authors, and [<sup>3sup>H]raclopride, a dopamine D<sub>2sub>/D<sub>3sub> antagonist, were used as radioligands. Our results demonstrate unchanged CB<sub>1sub>R density in the putamen and nucleus caudatus of deceased PD patients, treated with levodopa (l-DOPA). At the same time dopamine D<sub>2sub>/D<sub>3sub> receptors displayed significantly decreased density levels in case of PD putamen (control: 47.97 卤 10.00 fmol/g, PD: 3.73 卤 0.07 fmol/g (mean 卤 SEM), p &lt; 0.05) and nucleus caudatus (control: 30.26 卤 2.48 fmol/g, PD: 12.84 卤 5.49 fmol/g, p &lt; 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 CB<sub>1sub>R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB<sub>1sub>R 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 CB<sub>1sub>R population and a decreased dopamine D<sub>2sub>/D<sub>3sub> 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.