Electrophysiological effects of a cannabinoid on neural activity in the globus pallidus

The globus pallidus contains a dense distribution of cannabinoid receptors and appears to be a site of action of cannabinoids in the production of catalepsy. Single unit electrophysiology was used to explore the role of cannabinoid receptors in the globus pallidus of the rat. Intravenous injections of the potent and selective synthetic cannabinoid (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; up to 0.5 mg/kg, i.v.) inhibited the spontaneous firing of neurons in the globus pallidus. In a second set of experiments, WIN 55,212-2 antagonized the inhibition of pallidal firing produced by electrical stimulation of the striatum. The pharmacological specificity of the effects of WIN 55,212-2 on basal and evoked activity in the globus pallidus was demonstrated by the lack of effect of the inactive enantiomer WIN 55,212-3. These results indicate that cannabinoids may produce functionally opposite effects on spontaneous and evoked activity in the globus pallidus: a decrease in spontaneous firing and a decrease in the inhibition of firing produced by the striatopallidal projection.