Cannabinoid receptor agonist and antagonist effects on motor function in normal and 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP)-treated non-human primates

Rationale: Although cannabinoid effects on motor function have been extensi vely studied in rodents, the role of cannabinoids in regulating behavior in primates is relatively unknown. Objectives: We compared the effects of can nabinoid agonists and dopamine antagonists on unconditioned behaviors in cy nomolgus monkeys (Macaca fascicularis). We further investigated the therape utic potential of cannabinoid antagonists in a primate model of Parkinson's disease. Methods. Drugs were administered i.m., and sessions were videotap ed and rated by a "blind" observer using a rating scale. Results: The dopam ine antagonist haloperidol decreased locomotor activity and increased brady kinesia in three subjects. Haloperidol also produced a dose-dependent incre ase in freezing and catalepsy in two out of the three subjects. The cannabi noid agonist levonantradol dose-dependently decreased general and locomotor activity and increased bradykinesia. In contrast to haloperidol, levonantr adol failed to produce freezing or catalepsy. At the dose range studied, te trahydrocannabinol did not affect general or locomotor activity, but increa sed bradykinesia. In view of the psychomotor slowing induced by cannabinoid agonists, we investigated the therapeutic potential of the cannabinoid rec eptor antagonist SR141716A in an early and advanced stage of 1-methyl-4-phe nyl-1,2,5,6-tetrahydropyridine-induced parkinsonism. In both models of Park inson's disease, SR141716A failed to alleviate the motor deficits of parkin sonism. Conclusions: Cannabinoid agonists do not induce catalepsy in primat es, a finding that differs from their effects in rodents. The primate may b e more suitable than rodents for predicting the effects of cannabinoids and their therapeutic potential on select primate behaviors.