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.