Detection of cannabinoid receptors CB1 and CB2 within basal ganglia output neurons in macaques: changes following experimental parkinsonism

Although type 1 cannabinoid receptors (CB(1)Rs) are expressed abundantly throughout the brain, the presence of type 2 cannabinoid receptors (CB(2)Rs) in neurons is still somewhat controversial. Taking advantage of newly designed CB(1)R and CB(2)R 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 CB(1)Rs and CB(2)Rs, as well as CB(1)R–CB(2)R heteromers within basal ganglia output neurons in all animal groups (control, parkinsonian and dyskinetic macaques). A marked reduction in the number of CB(1)Rs, CB(2)Rs and CB(1)R–CB(2)R heteromers was found in dyskinetic animals, mimicking the observed reduction in CB(1)R and CB(2)R mRNA expression levels. The fact that chronic levodopa treatment disrupted CB(1)R–CB(2)R heteromeric complexes should be taken into consideration when designing new drugs acting on cannabinoid receptor heteromers.