Pharmacological blockade of TRPV1 receptors modulates the effects of 6-OHDA on motor and cognitive functions in a rat model of Parkinson's disease.

TRPV1 receptors and cannabinoid system are considered as important modulators of basal ganglia functions, and their pharmacologic manipulation represents a promising therapy to alleviate Parkinson-induced hypokinesia. Recent evidence suggests that the blockade of cannabinoid receptors might be beneficial to alleviate motor deficits observed in Parkinson's disease. In the present study, we have evaluated the effects of AMG9810 , a selective antagonist of TRPV1 receptors, on the motor and cognitive functions in a rat model of Parkinson's disease generated by an intracerebroventricular injection of 6- hydroxydopamine (6-OHDA) (200 μg per animal). The injection of 10 nmol of AMG9810 for a single dose (AMG1) and for 2 weeks (AMG14) partially attenuated the hypokinesia shown by these animals in motor function evaluation tests, whereas chronic administration of AMG had destructive effects on learning and memory in 6-OHDA-treated rats. Animals in the AMG 1 and AMG 14 groups showed an increased latency to fall in rotarod and grasping tests in each trials compared with 6-OHDA-treated rats (P < 0.01) and DMSO 1 and 14 groups (P < 0.05). Our data indicate that pharmacological blockade of TRPV1 receptors by AMG 9810 attenuates the hypokinetic effects of 6-OHDA and that TRPV1 receptors play an important role in 6-OHDA-induced hypokinesia, although elucidation of the neurochemical substrate involved in this process remains a major challenge for the future.