Local effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus

Abstract

The globus pallidus has been identified as a site of action for the motor effects of cannabinoids. A previous report from this laboratory demonstrated that systemic administration of the potent and selective cannabinoid receptor agonist ( R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpholinyl) methyl]pyrrolo[1,2,3- de]-1,4-benzoxazin-6-yl] (1-napthalenyl) methanone (WIN 55,212-2) inhibits rat pallidal neurons and reverses the inhibition of pallidal activity produced by electrical stimulation of the striatum. The current study used in vivo single unit electrophysiology/micropressure ejection to investigate whether the effects of cannabinoids on spontaneous activity and evoked inhibition in the globus pallidus are locally mediated. Micropressure ejection of either WIN 55,212-2 or CP 55,940 into the globus pallidus inhibited spontaneous activity in the globus pallidus. Local administration of the cannabinoid receptor antagonist, N-piperidino-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamide (SR141716A), did not produce an effect on its own but blocked the effect of WIN 55,212-2 on spontaneous activity of pallidal neurons. The decrease in pallidal activity produced by WIN 55,212-2 was not blocked by coadministration of bicuculline, suggesting this effect is independent of GABA A receptors. Micropressure ejection of cannabinoids into the globus pallidus did not reverse the inhibitory effect of striatal stimulation in the globus pallidus. Taken together, these findings suggest that pallidal cannabinoid receptors mediate an inhibition of spontaneous activity in the globus pallidus.