Abstract |
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.
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Authors | Szabolcs Farkas, Katalin Nagy, Zhisheng Jia, Tibor Harkany, Miklós Palkovits, Sean R Donohou, Victor W Pike, Christer Halldin, Domokos Máthé, László Csiba, Balázs Gulyás |
Journal | Brain research bulletin
(Brain Res Bull)
Vol. 87
Issue 6
Pg. 504-10
(Apr 10 2012)
ISSN: 1873-2747 [Electronic] United States |
PMID | 22421165
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2012 Elsevier Inc. All rights reserved. |
Chemical References |
- 4-cyano-1-(2-iodophenyl)-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxamide
- Dopamine Antagonists
- Iodine Radioisotopes
- Pyrazoles
- Receptor, Cannabinoid, CB1
- Receptors, Dopamine D2
- Receptors, Dopamine D3
- Thiram
- Raclopride
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Topics |
- Aged
- Autoradiography
(methods)
- Case-Control Studies
- Caudate Nucleus
(diagnostic imaging, drug effects, metabolism)
- Dopamine Antagonists
(pharmacokinetics)
- Female
- Humans
- Iodine Radioisotopes
(pharmacokinetics)
- Male
- Parkinson Disease
(pathology)
- Protein Binding
(drug effects)
- Putamen
(diagnostic imaging, drug effects, metabolism)
- Pyrazoles
(pharmacokinetics)
- Raclopride
(pharmacokinetics)
- Radionuclide Imaging
- Receptor, Cannabinoid, CB1
(antagonists & inhibitors, metabolism)
- Receptors, Dopamine D2
(metabolism)
- Receptors, Dopamine D3
(metabolism)
- Thiram
(pharmacokinetics)
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