LOCAL-EFFECTS OF CANNABINOIDS ON SPONTANEOUS ACTIVITY AND EVOKED INHIBITION IN THE GLOBUS-PALLIDUS

The globus pallidus has been identified as a site of action for the mo tor effects of cannabinoids. A previous report from this laboratory de monstrated that systemic administration of the potent and selective ca nnabinoid :receptor agonist (R)-(+)-[2,3-dihydro-5-methyl-3-[(4-morpho linyl) methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl] (1-napthalenyl) m ethanone (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 electrophysi ology/micropressure ejection to investigate whether the effects of can nabinoids 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 act ivity in the globus pallidus. Local administration of the cannabinoid receptor antagonist, ,4-dichlorophenyl)-4-methyl-3-pyrazole-carboxamid e (SR141716A), did not produce an effect on its own but blocked the ef fect 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 indepen dent 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 su ggest that pallidal cannabinoid receptors mediate an inhibition of spo ntaneous activity in the globus pallidus. (C) 1998 Elsevier Science B. V. All rights reserved.