In vivo Bidirectional Modulation of Cannabinoid on the Activity of Globus Pallidus in Rats

Abstract

Endocannabinoids are bioactive substances which participate in central motor control. The globus pallidus (GP) is a major nucleus in the basal ganglia circuit, which plays an important function in movement regulation. Both cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R) are expressed in the GP suggesting GP as a main action area of endocannabinoids. To investigate the direct electrophysiological and behavioral effects of cannabinoids in GP, in vivo single unit extracellular recordings and behavioral tests were performed in rats. Administration of WIN 55,212-2 exerted three neuronal response patterns from all sampled neurons of GP, including (1) increase of the firing rate; (2) decrease of the firing rate; (3) increase and then decrease of the firing rate. Selectively blocking CB1R by AM 251 decreased the firing rate and increased the firing rate. Selectively blocking CB2R by AM 630 did not change the firing rate significantly, which suggested that endocannabinoids modulated the spontaneous firing activity of pallidal neurons mainly via CB1R. Furthermore, co-application of AM 251, but not AM 630, blocked WIN 55,212-2-induced modulation of firing activity of pallidal neurons. Finally, both haloperidol-induced postural behavioral test and elevated body swing test (EBST) showed that unilateral microinjection of WIN 55,212-2 mainly induced contralateral-biased swing and deflection behaviors. Meanwhile, AM 251 produced opposite effect. The present in vivo study revealed that cannabinoids produced complicated electrophysiological and behavioral effects in the GP, which further demonstrated that the GP is a major functional region of endocannabinoid.