Abstract
The involvement of striatal somatostatin receptors (sst1, sst2 and sst4) in locomotor activity was investigated. Male Sprague–Dawley rats, 280–350 g, received in the striatum bilateral infusions of saline, somatostatin, and selective sst1, sst2, and sst4 ligands. Spontaneous locomotor activity was recorded for 60 min. The involvement of excitatory amino acid receptors (AMPA and NMDA) on somatostatin’s actions was also examined. Western blot analysis was employed for the identification of somatostatin receptors in striatal membranes. Somatostatin, sst2 and sst4, but not sst1, selective ligands increased rat locomotor activity in a dose-dependent manner. Blockade of AMPA and NMDA receptors reversed somatostatin’s actions. In conclusion, striatal somatostatin receptor activation differentially influence rat locomotor activity, while glutamatergic actions underlie the behavioral actions of somatostatin.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aguado-Llera D, Puebla-Jiménez L, Yébenes-Gregorio L et al (2008) Alteration of the somatostatinergic system in the striatum of rats with acute experimental autoimmune encephalomyelitis. Neuroscience 148:238–249
Allen JP, Hathway GJ, Kendrick KM et al (2003) Somatostatin receptor 2 regulates motoric and anxiolytic effects in murine CNS. Eur J Neurosci 17:1881–1895
Brazeau P, Vale W, Burgus R et al (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 129:77–79
Chesselet MF, Reisine TD (1983) Somatostatin regulates dopamine release in rat striatal slices and cat caudate nuclei. J Neurosci 3:232–236
Epelbaum J (1986) Somatostatin in the central nervous system: physiological and pathological modifications. Prog Neurobiol 27:63–100
Fehlmann D, Langenegger D, Schuepbach E et al (2000) Distribution and characterisation of somatostatin receptor mRNA and binding sites in the brain and periphery. J Physiol (Paris) 94:265–281
Gerner RH, Yamada T (1982) Altered neuropeptide concentrations in cerebrospinal fluid of psychiatric patients. Brain Res 238:298–302
Hathway GJ, Emson PC, Humphrey PP et al (1998) Somatostatin potently stimulates in vivo striatal dopamine and gamma-aminobutyric acid release by a glutamate-dependent action. J Neurochem 70:1740–1749
Hathway GJ, Humphrey PP, Kendrick KM (1999) Evidence that somatostatin sst2 receptors mediate striatal dopamine release. Br J Pharmacol 128:1346–1352
Hathway GJ, Humphrey PP, Kendrick KM (2003) Somatostatin induces striatal dopamine release and contralateral turning behavior in the mouse. Neurosci Lett 358:127–131
Helboe L, Müller M, Nürreqaard L et al (1997) Development of selective antibodies against the human somatostatin receptor subtypes sst1-sst5. Brain Res Mol Brain Res 49:82–88
Hofland LJ, Liu Q, Van Koetsevld PM et al (1999) Immunohistochemical detection of somatostatin receptor subtypes sst1 and sst2A in human somatostatin receptor positive tumors. J Endocrinol Metab 84:775–780
Hoyer D, Bell GI, Berelowitz M et al (1995) Classification and nomenclature of somatostatin receptors. Trends Pharmacol Sci 16:86–88
Imperato A, Honore T, Jensen LH (1990) Dopamine release in the nucleus caudatus and in the nucleus accumbens is under glutamatergic control through non-NMDA receptors: a study in freely-moving rats. Brain Res 530:223–228
Kawaguchi Y, Wilson CJ, Augood SJ et al (1995) Striatal interneurones: chemical, physiological and morphological characterization. Trends Neurosci 18:527–535
Kendrick KM, Guevara-Guzman R, de la Riva C et al (1996) NMDA and kainate-evoked release of nitric oxide and classical transmitters in the rat striatum: in vivo evidence that nitric oxide may play a neuroprotective role. Eur J Neurosci 8:2619–2634
Kong H, DePaoli M, Breder CD et al (1994) Differential expression of messenger RNAs for somatostatin receptor subtypes SSTR1, SSTR2 and SSTR3 in adult rat brain: analysis by RNA blotting and in situ hybridization histochemistry. Neuroscience 59:175–184
Lu JQ, Stoessl AJ (2002) Somatostatin modulate the behavioral effects of dopamine receptor activation in parkinsonian rats. Neuroscience 112:261–266
Marazioti A, Kastellakis A, Antoniou K et al (2005) Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity. Psychopharmacology 181:319–327
Olias G, Viollet C, Kusserow H et al (2004) Regulation and function of somatostatin receptors. J Neurochem 89:1057–1091
Pallis E, Thermos K, Spyraki C (2001) Chronic desipramine treatment selectively potentiates somatostatin-induced dopamine release in the nucleus accumbens. Eur J Neurosci 14:763–767
Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Academic Press, New York
Raulf F, Pèrez J, Hoyer D et al (1994) Differential expression of five somatostatin receptor subtypes, SSTR1-5, in the CNS and peripheral tissue. Digestion 55:46–53
Raynor K, Lucki I, Reisine T (1993) Somatostatin receptors in the nucleus accumbens selectively mediate the stimulatory effect of somatostatin on locomotor activity in rats. J Pharmacol Exp Therapeutics 265:67–73
Schreff M, Schulz S, Händel M et al (2000) Distribution, targeting, and internalization of the sst4 somatostatin receptor in rat brain. J Neurosci 20:3785–3797
Schulz S, Händel M, Schreff M et al (2000) Localization of five somatostatin receptors in the rat central nervous system using subtype-specific antibodies. J Physiol (Paris) 94:259–264
Selmer IS, Schindler M, Humphrey PPA et al (2000) Immunohistochemical localization of the somatostatin sst4 receptor in rat brain. J Neurosci 98:523–533
Smolders I, Sarre S, Vanhaesendonck C et al (1996) Extracellular striatal dopamine and glutamate after decortication and kainate receptor stimulation, as measured by microdialysis. J Neurochem 66:2373–2380
Tashev R, Belcheva S, Milenov K et al (2001) Behavioral effects of somatostatin microinjected into caudate putamen. Neuropeptides 35:271–275
Tashev R, Belcheva S, Belcheva I (2004) Differential effects of somatostatin on exploratory behavior after unilateral injections into rat neostriatum. Peptides 25:123–128
Thermos K, Radke J, Kastellakis A et al (1996) Dopamine-somatostatin interactions in the rat striatum: An in vivo microdialysis study. Synapse 22:209–216
Thermos K, Bagnoli P, Epelbaum J et al (2006) The somatostatin sst1 receptor: an autoreceptor for somatostatin in brain and retina? Pharmacol Ther 110:455–464
Vasilaki A, Papasava D, Hoyer D et al (2004) The somatostatin receptor (sst(1)) modulates the release of somatostatin in the nucleus accumbens of the rat. Neuropharmacology 47:612–618
Vincent SR, Jonansson O (1983) Striatal neurons containing both somatostatin-and avian pancreatic polypeptide (APP)-like immunoreactivities and NADPH-diaphorase activity: a light and electron microscopic study. J Comp Neurol 217:264–270
Viollet C, Vaillend C, Videau C et al (2000) Involvement of sst2 somatostatin receptor in locomotor, exploratory activity and emotional reactivity in mice. Eur J Neurosci 12:3761–3770
Wheeler D, Boutelle MG, Fillenz M (1995) The role of N-methyl-d-aspartate receptors in the regulation of physiologically released dopamine. Neuroscience 65:767–774
Acknowledgements
This study was partially funded by the Graduate Program of Neuroscience [EPEAEK], Faculty of Medicine, University of Crete. We thank Merck laboratories for the L-ligands and Dr. D. Hoyer for the sst2 antagonist. The authors thank Ms. Eleni Renieri for excellent technical assistance and Ms. Foteini Kiagiadaki for her help with the art work.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Santis, S., Kastellakis, A., Kotzamani, D. et al. Somatostatin increases rat locomotor activity by activating sst2 and sst4 receptors in the striatum and via glutamatergic involvement. Naunyn-Schmied Arch Pharmacol 379, 181–189 (2009). https://doi.org/10.1007/s00210-008-0346-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00210-008-0346-z