THE CANNABINOID RECEPTOR AGONIST WIN-55,212-2 REDUCES D-2, BUT NOT D-1, DOPAMINE RECEPTOR-MEDIATED ALLEVIATION OF AKINESIA IN THE RESERPINE-TREATED RAT MODEL OF PARKINSONS-DISEASE

The effects of the synthetic cannabinoid receptor agonist WIN 55,212-2 on dopamine receptor-mediated alleviation of akinesia were evaluated in the reserpine-treated rat model of parkinsonism. The dopamine D-2 r eceptor agonist quinpirole (0.1 mg/kg, ip) caused a significant allevi ation of the akinesia, This effect was significantly reduced by coinje ction with the cannabinoid receptor agonist WIN 55,212-2 (0.1 and 0.3 mg/kg). The simultaneous administration of the cannabinoid receptor an tagonist SR 141716A (3 mg/kg, ip) with quinpirole and WIN 55,212-2 blo cked the effect of WIN 55,212-2 on quinpirole-induced alleviation of a kinesia, The selective dopamine D-1 receptor agonist chloro-APB (SKF82 958, 0.1 mg/kg) alleviated akinesia in a significant manner, WIN 55,21 2-2 (0.1-1 mg/kg, ip) did not affect the antiakinetic effect of chloro -APB. Combined injection of both D-1 and D-2 dopamine receptor agonist s (both at either 0.1 or 0.02 mg/kg) resulted in a marked synergism of the antiakinetic effect, WIN 55,212-2 (0.1-1 mg/kg) significantly red uced the antiakinetic effect of combined injections of quinpirole and chloro-APB at both 0.1 and 0.02 mg/kg. The effect of 0.3 mg/kg WIN 55, 212-2 on combined D-1 and D-2 agonist-induced locomotion (0.02 mg/kg) was blocked by SR 141761A (3 mg/kg), Neither WIN 55,212-2 alone (0.1 a nd 0.3 mg/kg) nor SR 141716A (3 and 30 mg/kg) alone had an antiparkins onian effect, These results suggest that cannabinoids may modulate neu rotransmission in the pathway linking the striatum indirectly to basal ganglia outputs via the lateral globus pallidus and the subthalamic n ucleus. (C) 1997 Academic Press.