Motor actions of cannabinoids in the basal ganglia output nuclei

The levels of CB1 cannabinoid receptors in the basal ganglia are the highes t in the. brain, comparable to the levels of dopamine receptors, a major tr ansmitter in the basal ganglia. This localization of receptors is consisten t with the profound effects on motor function exerted by cannabinoids. The output nuclei of the basal ganglia, the globus pallidus (GP) and substantia nigra reticulata (SNr), apparently lack intrinsic cannabinoid receptors. R ather, the receptors are located on afferent terminals, the striatum being the major source. Cannabinoids blocked the inhibitory action of the striata l input in the SNr. Furthermore, cannabinoids blocked the excitatory effect of stimulation of the subthalamic input to the SNr revealing, along with d ata from in situ hybridization studies, that this input is another likely s ource of cannabinoid receptors to the SNr. Similar actions of cannabinoids were observed in the GP. Behavioral studies further revealed that the actio n of cannabinoids differs depending upon which input to the output nuclei o f the basal ganglia is active. The inhibitory striatal input is quiescent a nd the cannabinoid action is observable only upon stimulation of the striat um, while the noticeable effect of cannabinoids under basal conditions woul d be on the tonically active subthalamic input. These data suggest that the recently discovered endogenous cannabinergic system exerts a major modulat ory action in the basal ganglia by its ability to block both the major exci tatory and inhibitory inputs to the SNr and GP.