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 microl per side) or the following selective ligands: L-797,591 (sst(1) analog, 60, 120, 240 ng/0.5 microl per side), L-779,976 (sst(2) analog, 120, 240, 480 ng/0.5 microl per side), L-803,087 (sst(4) analog; 120, 240, 480 ng/0.5 microl per side), L-796,778 (sst(3) analog, 240 ng/0.5 microl per side), SRA-880 (sst(1) selective antagonist + somatostatin, 120 ng/0.5 microl per side), CYN154806 (sst(2) selective antagonist + somatostatin, 120 ng/0.5 microl 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.