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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 selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015.
Brain Res Bull. 2012 Apr 10; 87(6):504-10.BR

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.

Authors+Show Affiliations

Department of Neurology, University of Debrecen, H-4012 Debrecen, Hungary.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22421165

Citation

Farkas, Szabolcs, et al. "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 Selective Dopamine D₂/D₃ Antagonist [³H]raclopride and the Novel CB₁ Inverse Agonist [¹²⁵I]SD7015." Brain Research Bulletin, vol. 87, no. 6, 2012, pp. 504-10.
Farkas S, Nagy K, Jia Z, et al. 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 selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015. Brain Res Bull. 2012;87(6):504-10.
Farkas, S., Nagy, K., Jia, Z., Harkany, T., Palkovits, M., Donohou, S. R., Pike, V. W., Halldin, C., Máthé, D., Csiba, L., & Gulyás, B. (2012). 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 selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015. Brain Research Bulletin, 87(6), 504-10. https://doi.org/10.1016/j.brainresbull.2012.02.012
Farkas S, et al. 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 Selective Dopamine D₂/D₃ Antagonist [³H]raclopride and the Novel CB₁ Inverse Agonist [¹²⁵I]SD7015. Brain Res Bull. 2012 Apr 10;87(6):504-10. PubMed PMID: 22421165.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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 selective dopamine D₂/D₃ antagonist [³H]raclopride and the novel CB₁ inverse agonist [¹²⁵I]SD7015. AU - Farkas,Szabolcs, AU - Nagy,Katalin, AU - Jia,Zhisheng, AU - Harkany,Tibor, AU - Palkovits,Miklós, AU - Donohou,Sean R, AU - Pike,Victor W, AU - Halldin,Christer, AU - Máthé,Domokos, AU - Csiba,László, AU - Gulyás,Balázs, Y1 - 2012/03/07/ PY - 2012/02/27/received PY - 2012/02/28/accepted PY - 2012/3/17/entrez PY - 2012/3/17/pubmed PY - 2012/7/24/medline SP - 504 EP - 10 JF - Brain research bulletin JO - Brain Res Bull VL - 87 IS - 6 N2 - 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. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/22421165/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_selective_dopamine_D₂/D₃_antagonist_[³H]raclopride_and_the_novel_CB₁_inverse_agonist_[¹²⁵I]SD7015_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(12)00043-3 DB - PRIME DP - Unbound Medicine ER -