Involvement of subthalamic nucleus in the stimulatory effect of Δ9-tetrahydrocannabinol on dopaminergic neurons

The cannabinoid CB1 receptor which is densely located in the basal ganglia is known to participate in the regulation of movement. The present study sought to determine the mechanisms underlying the effect of Δ9-tetrahydrocannabinol (Δ9-THC) on neurons in the substantia nigra pars compacta (SNpc) using single-unit extracellular recordings in anesthetized rats. Administration of Δ9-THC (0.25–2 mg/kg, i.v.) increased the firing rate of SNpc neurons (maximal effect: 33.54±6.90%, n=8) without modifying other firing parameters (coefficient of variation and burst firing). This effect was completely blocked by the cannabinoid receptor antagonist rimonabant (0.5 mg/kg, i.v.). In addition, the blockade of excitatory amino acids receptors by kynurenic acid (0.5 μM, i.c.v.) or a chemical lesion of the subthalamic nucleus (STN) with ibotenic acid abolished Δ9-THC effect. These results indicate that CB1 receptor activation modulates SNpc neuronal activity by an indirect mechanism involving excitatory amino acids, probably released from STN axon terminals in the SNpc.