The decrease of dopamine D 2/D 3 receptor densities in the putamen and nucleus caudatus goes parallel with maintained levels of CB 1 cannabinoid receptors in Parkinson's disease: A preliminary autoradiographic study with the selective dopamine D 2/D 3 antagonist [ 3H]raclopride and the novel CB 1 inverse agonis

Szabolcs Farkas, Katalin Nagy, Zhisheng Jia, Tibor Harkany, Miklós Palkovits, Sean R. Donohou, Victor W. Pike, Christer Halldin, Domokos Máthé, László Csiba, Balázs Gulyás

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)504-510
Number of pages7
JournalBrain Research Bulletin
Volume87
Issue number6
DOIs
Publication statusPublished - Apr 10 2012

Keywords

  • Dopamine D /D receptor
  • Endocannabinoid CB1 receptor
  • Human brain autoradiography
  • Molecular imaging biomarker
  • Parkinson's disease
  • Striatum

ASJC Scopus subject areas

  • Neuroscience(all)

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