Role of the subthalamic nucleus in cannabinoid actions in the substantia nigra of the rat

The effect of cannabinoids on the excitatory input to the substantia nigra reticulata (SNr) from the subthalamic nucleus was explored. For this purpose a knife cut was performed rostral to the subthalamic nucleus to isolate the subthalamic nucleus and the SNr from the striatum, a major source of cannabinoid receptors to the SNr. The data showed that the cannabinoid agonist WIN55,212-2 blocked the increase in the firing rate of SNr neurons induced by stimulation of the subthalamic nucleus with bicuculline. Furthermore, the cannabinoid antagonist SR141716A antagonized the effect of the cannabinoid agonist. This study showed that cannabinoids regulate not only the striatonigral pathway, as previously reported, but also the subthalamonigral pathway. The opposite influences of these two inputs to the SNr, inhibitory and excitatory respectively, suggest that endogenous cannabinoids play a major role in the physiological regulation of the SNr.