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

Cannabinoid type-1 receptors (CB1 Rs) modulate synaptic neurotransmission by participating in retrograde signaling in the adult brain. Increasing evidence suggests that cannabinoids through CB1 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 CB1 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 CB1 R and dopamine D-2/D-3 receptor autoradiography. [I-125]SD7015, a novel selective CB1 R inverse agonist, developed by a number of the present co-authors, and [H-3]raclopride, a dopamine D-2/D-3 antagonist, were used as radioligands. Our results demonstrate unchanged CB1 R 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 +/- 10.00 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 CB1 R population even in late stages of levodopa treated PD. This further supports the presence of an intact CB1 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 CB1 R 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. (C) 2012 Elsevier Inc. All rights reserved.