Activation of somatostatin receptors in the globus pallidus increases rat locomotor activity and dopamine release in the striatum

Rationale Somatostatin and its receptors have been localized in brain nuclei implicated in motor control, such as the striatum, nucleus accumbens, ventral pallidum, and globus pallidus (GP). Objectives The objective of this study was to investigate the role of somatostatin receptors (sst 1,2,4 ) in the GP on dopamine (DA)-mediated behaviors, such as locomotor activity, and to examine the GP–striatum circuitry by correlating the effect of somatostatin in the GP with the release of DA in the striatum. Materials and methods Animals received saline, somatostatin (60, 120, 240 ng/0.5 μl per side) or the following selective ligands: L-797,591 (sst 1 analog, 60, 120, 240 ng/0.5 μl per side), L-779,976 (sst 2 analog, 120, 240, 480 ng/0.5 μl per side), L-803,087 (sst 4 analog; 120, 240, 480 ng/0.5 μl per side), L-796,778 (sst 3 analog, 240 ng/0.5 μl per side), SRA-880 (sst 1 selective antagonist + somatostatin, 120 ng/0.5 μl per side), CYN154806 (sst 2 selective antagonist + somatostatin, 120 ng/0.5 μl per side) bilaterally in the GP of the rat. Locomotor activity was measured for 60 min. The effect of somatostatin, administered intrapallidally, on the extracellular concentrations of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the striatum was also studied in the behaving rat using in vivo microdialysis methodology. Results Somatostatin increased the locomotor activity of the rat in a dose-dependent manner. This effect was mediated by activation of the sst 1 , sst 2 , and sst 4 receptors. Selective sst agonists increased locomotor activity in a statistical significant manner, while selective sst 1 and sst 2 antagonists reversed the somatostatin-mediated locomotor activity to control levels. DA levels increased in the striatum after intrapallidal infusion of somatostatin (240 ng/side). Conclusions These data provide behavioral and neurochemical evidence of the functional role of somatostatin receptors in the GP–striatum circuitry.