Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity

Abstract

Rationale: Somatostatin and its receptors (sst(1) and sst(2)) have been localized in brain nuclei implicated in motor control, such as the nucleus accumbens, ventral pallidum (VP) and substantia innominata (SI).

Objectives: The objective of the study is to investigate the effect of somatostatin and selective sst(1) and sst(2) analogs infused in the VP/SI on the locomotor activity of the rat.

Methods: Somatostatin (15, 30, 60, 120 and 240 ng/0.5 microl/side), CH275 (sst(1) analog; 60, 180, 240 and 480 ng/0.5 microl/side), MK678 (sst(2) analog; 120, 240 and 480 ng/0.5 microl/side), L-809,087 (sst(4) agonist, 240 ng/0.5 microl/side) or saline (vehicle) were infused bilaterally in the VP/SI of the rat and locomotor activity measured for 60 min. The effect of SRA-880 (sst(1) antagonist) and CYN-154806 (sst(2) antagonist) on somatostatin-, CH275- and MK678-mediated locomotor activity was also ascertained.

Results: Somatostatin decreased locomotor activity in the first 30 min after its infusion in the VP/SI and in a dose-dependent manner. The sst(1) and sst(2) antagonists, SRA-880 and CYN-154806, respectively, reversed the somatostatin effect. The sst(1) and sst(2) agonists CH275 and MK678, respectively, mimicked somatostatin's actions, while the selective sst(4) agonist L-809,087 had no effect. Moreover, SRA-880 and CYN-154806 reversed the respective agonist action on locomotor activity.

Conclusion: The present study provides functional evidence for the presence of sst(1) and sst(2) receptors in the VP/SI and their implication in motor control. The mechanism via which somatostatin and agonists mediate the attenuation of locomotor activity is presently being investigated.