Abstract Although type 1 cannabinoid receptors (CB1-
Rs) are expressed abundantly throughout the brain, the
presence of type 2 cannabinoid receptors (CB2Rs) in neurons
is still somewhat controversial. Taking advantage of
newly designed CB1R and CB2R mRNA riboprobes, we
demonstrate by PCR and in situ hybridization that transcripts
for both cannabinoid receptors are present within
labeled pallidothalamic-projecting neurons of control and
MPTP-treated macaques, whereas the expression is markedly
reduced in dyskinetic animals. Moreover, an in situ
proximity ligation assay was used to qualitatively assess
the presence of CB1Rs and CB2Rs, as well as CB1R–CB2R
heteromers within basal ganglia output neurons in all
animal groups (control, parkinsonian and dyskinetic
macaques). A marked reduction in the number of CB1Rs,
CB2Rs and CB1R–CB2R heteromers was found in dyskinetic
animals, mimicking the observed reduction in CB1R
and CB2R mRNA expression levels. The fact that chronic
levodopa treatment disrupted CB1R–CB2R heteromeric
complexes should be taken into consideration when
designing new drugs acting on cannabinoid receptor
heteromers