The decrease of dopamine D₂/D₃ receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB₁ cannabinoid receptors in Parkinson's disease: A preliminary autoradiographic study with the

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• 作者：Szabolcs Farkas^a ; Katalin Nagy^a ; Zhisheng Jia^b ; Tibor Harkany^c ; Mikló ; s Palkovits^d ; Sean R. Donohou^e ; Victor W. Pike^e ; Christer Halldin^b ; Domokos M&#225 ; thé ; ^f ; ^g ; L&#225 ; szló ; Csiba^a ; ¹ ; Bal&#225 ; zs Guly&#225 ; s^b ; ¹ ; ^{balazs.gulyas@ki.se}
• 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 (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 卤 10.00 fmol/g, PD: 3.73 卤 0.07 fmol/g (mean 卤 SEM), p < 0.05) and nucleus caudatus (control: 30.26 卤 2.48 fmol/g, PD: 12.84 卤 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.