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

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Abstract

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 (sst1,2,4) 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 (sst1 analog, 60, 120, 240 ng/0.5 μl per side), L-779,976 (sst2 analog, 120, 240, 480 ng/0.5 μl per side), L-803,087 (sst4 analog; 120, 240, 480 ng/0.5 μl per side), L-796,778 (sst3 analog, 240 ng/0.5 μl per side), SRA-880 (sst1 selective antagonist + somatostatin, 120 ng/0.5 μl per side), CYN154806 (sst2 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 sst1, sst2, and sst4 receptors. Selective sst agonists increased locomotor activity in a statistical significant manner, while selective sst1 and sst2 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.

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Acknowledgments

The authors would like to thank Dr. D. Hoyer for his kind gifts of SRA-880 and CYN-154806 and Merck Laboratories (Rahway, N.J.) for the L-analogs. This work was supported by a grant from the Greek Ministry of Education (Program Heraklitos to K.T.). The authors have no financial relationship with the above mentioned organization. We declare that the experiments comply with the current laws of Greece (EEC Council 86/609; 27/01/1992, No 116).

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Authors and Affiliations

  1. Department of Basic Sciences, Laboratory of Pharmacology, University of Crete, Faculty of Medicine, Heraklion, Crete, 71110, Greece

    A. Marazioti & K. Thermos

  2. Laboratory of Pharmacology, School of Medicine, University of Athens, Athens, Greece

    A. Marazioti, P. M. Pitychoutis, Z. Papadopoulou-Daifoti & C. Spyraki

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  1. A. Marazioti
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  2. P. M. Pitychoutis
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  3. Z. Papadopoulou-Daifoti
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  5. K. Thermos
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Correspondence to K. Thermos.

Additional information

We announce with great sorrow that our colleague and friend Prof. Christina Spyraki passed away on September 2, 2006.

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Marazioti, A., Pitychoutis, P.M., Papadopoulou-Daifoti, Z. et al. Activation of somatostatin receptors in the globus pallidus increases rat locomotor activity and dopamine release in the striatum. Psychopharmacology 201, 413–422 (2008). https://doi.org/10.1007/s00213-008-1305-6

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  • DOI: https://doi.org/10.1007/s00213-008-1305-6

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