Skip to main content
Log in

Anxiolytic and antidepressant actions of somatostatin: the role of sst2 and sst3 receptors

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale and objectives

Somatostatin is a cyclic polypeptide that inhibits the release of a variety of regulatory hormones (e.g., growth hormone, insulin, glucagon, and thyrotropin). Somatostatin is also widely distributed within the central nervous system (CNS), acting both as a neurotransmitter and as a neuromodulator. Recently, we showed that intracerebroventricular (i.c.v.) administration of somatostatin reduced anxiety-like and depression-like behaviors in animal models. The somatostatin receptor subtypes that are involved in these behavioral effects, however, have not been investigated. In the CNS, the neurotransmitter actions of somatostatin are mediated through five G-protein coupled receptors (sst1 to sst5).

Materials and methods

We examined the behavioral effects of i.c.v. microinfusions of different doses of selective agonists of each of the five somatostatin receptor subtypes. Their behavioral effects were assessed in the elevated plus-maze and the forced swim apparatus, rodent models of anxiolytic and antidepressant drug effects, respectively.

Results

Anxiety-like behavior was reduced following i.c.v. infusions of a selective sst2 receptor agonist, but not after infusions of the other four receptor agonists. An antidepressant-like effect was observed following infusions of either sst2 or sst3 agonists.

Conclusions

The results add to our nascent understanding of the role of somatostatin in anxiety- and depression-like behavior and suggest a clinical role for somatostatin agonists for the simultaneous treatment of anxiety and depression, which are often comorbid.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Baraban SC, Tallent MK (2004) Interneuron diversity series: interneuronal neuropeptides—endogenous regulators of neuronal excitability. Trends Neurosci 27:135–142

    Article  PubMed  CAS  Google Scholar 

  • Beranek L, Obal F, Taishi P, Bodosi B, Laczi F, Krueger JM (1997) Changes in rat sleep after single and repeated injections of the long-acting somatostatin analog octreotide. Am J Physiol Regul Integr Comp Physiol 273:R1484–R1491

    CAS  Google Scholar 

  • Betoin F, Ardid D, Herbet A, Aumaitre O, Kemeny JL, Duchenemarullaz P, Lavarenne J, Eschalier A (1994) Evidence for a central long-lasting antinociceptive effect of vapreotide, an analog of somatostatin, involving an opioidergic mechanism. J Pharmacol Exp Ther 269:7–14

    PubMed  CAS  Google Scholar 

  • Binaschi A, Bregola G, Simonato M (2003) On the role of somatostatin in seizure control: clues from the hippocampus. Rev Neurosci 14:285–301

    PubMed  CAS  Google Scholar 

  • Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79

    Article  PubMed  CAS  Google Scholar 

  • Breder CD, Yamada Y, Yasuda K, Seino S, Saper CB, Bell GI (1992) Differential expression of somatostatin receptor subtypes in brain. J Neurosci 12:3920–3934

    PubMed  CAS  Google Scholar 

  • Buckmaster PS, Otero-Corchon V, Rubinstein M, Low MJ (2002) Heightened seizure severity in somatostatin knockout mice. Epilepsy Res 48:43–56

    Article  PubMed  CAS  Google Scholar 

  • Carlton SM, Du JH, Zhou ST, Coggeshall RE (2001) Tonic control of peripheral cutaneous nociceptors by somatostatin receptors. J Neurosci 21:4042–4049

    PubMed  CAS  Google Scholar 

  • Carlton SA, Zhou ST, Du JH, Hargett GL, Ji GC, Coggeshall RE (2004) Somatostatin modulates the transient receptor potential vanilloid 1 (TRPV1) ion channel. Pain 110:616–627

    Article  PubMed  CAS  Google Scholar 

  • Cervia D, Casini G, Bagnoli P (2008) Physiology and pathology of somatostatin in the mammalian retina: a current view. Mol Cell Endocrinol 286:112–122

    Article  PubMed  CAS  Google Scholar 

  • Chesselet MD, Reisine T (1983) Somatostatin regulates dopamine release in rat striatal slices and cat caudate nuclei. J Neurosci 3:232–236

    PubMed  CAS  Google Scholar 

  • Chrubasik S, Ziegler R (1996) Does the somatostatin analogue pctreotide have a role in pain relief? Pain Clin 8:369–375

    Google Scholar 

  • Danguir J (1986) Intracerebroventricular infusion of somatostatin selectively increases paradoxical sleep in rats. Brain Res 367:26–30

    Article  PubMed  CAS  Google Scholar 

  • De Jong M, Breeman WAP, Bernard HF, Kooij PPM, Slooter GD, Van Eijck CHJ, Kwekkeboom DJ, Valkema R, Macke HR, Krenning EP (1999) Therapy of neuroendocrine tumors with radiolabeled somatostatin-analogues. Quart J Nucl Med 43:356–366

    Google Scholar 

  • Detke M, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially activated by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72

    Article  PubMed  CAS  Google Scholar 

  • Dournaud P, JazatPoindessous F, Slama A et al (1996) Correlations between water maze performance and cortical somatostatin mRNA and high-affinity binding sites during ageing in rats. Eur J NeuroSci 8:476–485

    Article  PubMed  CAS  Google Scholar 

  • Dournaud P, Slama A, Beaudet A et al (2000) Somatostatin receptors. In: Quirion R, Björklund A, Hökfelt T (eds) Handbook of chemical neuroanatomy. Elsevier, Amsterdam, pp 1–43

    Google Scholar 

  • Dutar P, Vaillend C, Viollet C, Billard JM, Potier B, Carlo AS, Ungerer A, Epelbaum J (2002) Spatial learning and hippocampal plasticity in type 2 somatostatin receptor knock-out mice. Neuroscience 112:455–466

    Article  PubMed  CAS  Google Scholar 

  • Dyer K, Cain DP (2007) Water maze impairments after combined depletion of somatostatin and serotonin in the rat. Behav Brain Res 181:85–95

    Article  PubMed  CAS  Google Scholar 

  • Engin E, Treit D (2008a) Dissociation of the anxiolytic-like effects of Avpr1a and Avpr1b receptor antagonists in the dorsal and ventral hippocampus. Neuropeptides 42:411–421

    Article  PubMed  CAS  Google Scholar 

  • Engin E, Treit D (2008b) The effects of intra-cerebral drug infusions on animals’ unconditioned fear reactions: a systematic review. Prog Neuro-psychopharmacol Biol Psychiatry 32:1399–1419

    Article  CAS  Google Scholar 

  • Engin E, Stellbrink J, Treit D et al (2008) Anxiolytic and antidepressant effects of intracerebroventricularly administered somatostatin: behavioral and neurophysiological evidence. Neuroscience 157:666–676

    Article  PubMed  CAS  Google Scholar 

  • Engin E, Treit D, Dickson CT (2009) Anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. Neuroscience 161(2):359–369

    Article  PubMed  CAS  Google Scholar 

  • Esclapez M, Houser CR (1995) Somatostatin neurons are a subpopulation of GABA neurons in the rat dentate gyrus - evidence from colocalization of pre-prosomatostatin and glutamate-decarboxylase messenger mRNAs. Neuroscience 64:339–355

    Article  PubMed  CAS  Google Scholar 

  • Fendt M, Koch M, Schnitzler HU (1996) Somatostatin in the pontine reticular formation modulates fear potentiation of the acoustic startle response: an anatomical, electrophysiological, and behavioral study. J Neurosci 16:3097–3103

    PubMed  CAS  Google Scholar 

  • Frieboes RM, Murck H, Shier T et al (1997) Somatostatin impairs sleep in elderly human subjects. Neuropsychopharmacology 16:339–345

    Article  PubMed  CAS  Google Scholar 

  • Gastambide F, Viollet C, Lepousez G, Epelbaum J, Guillou JL (2009) Hippocampal somatostatinR4 somatostatin receptors control the selection of memory strategies. Psychopharmacology 202:153–163

    Article  PubMed  CAS  Google Scholar 

  • Gheorvassaki EG, Thermos K, Liapakis G, Spyraki C (1992) Effects of acute and chronic desipramine treatment on somatostatin receptors in brain. Psychopharmacology 108:363–366

    Article  PubMed  CAS  Google Scholar 

  • Hajdu I, Szentirmai E, Obal F, Krueger JM (2003) Different brain structures mediate drinking and sleep suppression elicited by the somatostatin analog, octreotide, in rats. Brain Res 994:115–123

    Article  PubMed  CAS  Google Scholar 

  • Händel M, Schulz S, Stanarius A, Schreff M, Erdtmann-Vourliotis M, Schmidt H, Wolf G, Höllt V (1999) Selective targeting of somatostatin receptor 3 to neuronal cilia. Neuroscience 89:909–926

    Article  PubMed  Google Scholar 

  • Hathway GJ, Humphrey PPA, Kendrick KM (2004) Somatostatin induces striatal dopamine release and contralateral turning behaviour in the mouse. Neurosci Lett 358:127–131

    Article  PubMed  CAS  Google Scholar 

  • Hervieu G, Emson PC (1999) Visualisation of somatostatin receptor sst3 in the rat central nervous system. Mol Brain Res 71:290–303

    Article  PubMed  CAS  Google Scholar 

  • Hofland LJ, Vankoetsveld PM, Wouters N, Waaijers M, Reubi JC, Lamberts SWJ (1992) Dissociation of antiproliferative and antihormonal effects of the somatostatin analog octreotide on 7315B pituitary tumor cells. Endocrinology 131:571–577

    Article  PubMed  CAS  Google Scholar 

  • Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54:21–30

    Article  PubMed  CAS  Google Scholar 

  • Holloway S, Feniuk W, Kidd EJ, Humphrey PPA (1996) A quantitative autoradiographical study on the distribution of somatostatin sst(2) receptors in the rat central nervous system using [I-125]-BIM-23027. Neuropharmacology 35:1109–1120

    Article  PubMed  CAS  Google Scholar 

  • Izquierdo-Claros RM, Boyano-Adanez MD, Torrecillas G et al (2001) Acute modulation of somatostatin receptor function by melatonin in the rat frontoparietal cortex. J Pineal Res 31:46–56

    Article  PubMed  CAS  Google Scholar 

  • Jiang N, Furue H, Katafuchi T, Yoshimura M (2003) Somatostatin directly inhibits substantia gelatinosa neurons in adult rat spinal dorsal horn in vitro. Neurosci Res 47:97–107

    Article  PubMed  CAS  Google Scholar 

  • Justino L, Welner SA, Tannenbaum GS, Schipper HM (1997) Long-term effects of cysteamine on cognitive and locomotor behavior in rats: relationship to hippocampal glial pathology and somatostatin levels. Brain Res 761:127–134

    Article  PubMed  CAS  Google Scholar 

  • Kluge C, Stoppel C, Szinyei C, Stork O, Pape HC (2008) Role of the somatostatin system in contextual fear memory and hippocampal synaptic plasticity. Learn Memory 15:252–260

    Article  CAS  Google Scholar 

  • Kong H, Depaoli AM, Breder CD, Yasuda K, Bell GI, Reisine T (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

    Article  PubMed  CAS  Google Scholar 

  • Korte M, De Boer SF (2003) A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze. Eur J Pharmacol 463:163–175

    Article  PubMed  CAS  Google Scholar 

  • Lamirault L, Guillou JL, Micheau J, Jaffard R (2001) Intrahippocampal injections of somatostatin dissociate acquisition from the flexible use of place responses. Eur J NeuroSci 14:567–570

    Article  PubMed  CAS  Google Scholar 

  • Lanneau C, Peineau S, Petit F, Epelbaum J, Gardette R (2000) Somatostatin modulation of excitatory synaptic transmission between periventricular and arcuate hypothalamic nuclei in vitro. J Neurophysiol 84:1464–1474

    PubMed  CAS  Google Scholar 

  • Llorenscortes C, Bertherat J, Jomary C, Kordon C, Epelbaum J (1992) Regulation of somatostatin synthesis by GABAA receptor stimulation in mouse brain. Mol Brain Res 13:277–282

    Article  CAS  Google Scholar 

  • Low MJ, Juarez R, Rubinstein M, Carey K (1998) Impaired learning and memory in somatostatin-deficient mice. Brain Res 809:P311

    Google Scholar 

  • Marazioti A, Kastellakis A, Antoniou K, Papasava D, Thermos K (2005) Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity. Psychopharmacology 181:319–326

    Article  PubMed  CAS  Google Scholar 

  • Marazioti A, Spyraki C, Thermos K (2006) Somatostatin (SRIF) infused in the globus pallidus increases locomotor activity and cFos expression in rat brain areas implicated in motor control. Acta Pharmacol Sin 27:S428

    Google Scholar 

  • Marazioti A, Pitychoutis PM, Papadopoulou-Daifoti Z, Spyraki C, Thermos K (2008) Activation of somatostatin receptors in the globus pallidus increases rat locomotor activity and dopamine release in the striatum. Psychopharmacology 201:413–422

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka N, Maeda N, Yamaguchi I et al (1994) Possible involvement of brain somatostatin in the memory formation of rats and the cognitive enhancing action of fr121196 in passive-avoidance task. Brain Res 642:11–19

    Article  PubMed  CAS  Google Scholar 

  • Matsuoka N, Yamazaki M, Yamaguchi I (1995) Changes in brain somatostatin in memory-deficient rats: comparison with cholinergic markers. Neuroscience 66:617–626

    Article  PubMed  CAS  Google Scholar 

  • Mazarati AM, Telegdy G (1992) Effects of somatostatin and antisomatostatin serum on picrotoxin-kindled seizures. Neuropharmacology 31:793–797

    Article  PubMed  CAS  Google Scholar 

  • McDonald AJ, Mascagni F (2002) Immunohistochemical characterization of somatostatin containing interneurons in the rat basolateral amygdala. Brain Res 943:237–244

    Article  PubMed  CAS  Google Scholar 

  • McEown K, Treit D (2009) The role of the dorsal and ventral hippocampus in fear and memory of a shock-probe experience. Brain Res 1251:185–194

    Article  PubMed  CAS  Google Scholar 

  • McNaughton N, Kocsis B, Hajos M (2007) Elicited hippocampal theta rhythm: a screen for anxiolytic and procognitive drugs through changes in hippocampal function? Behav Pharmacol 18:329–346

    Article  PubMed  CAS  Google Scholar 

  • Meis S, Sosulina L, Schulz S et al (2005) Mechanisms of somatostatin-evoked responses in neurons of the rat lateral amygdala. Eur J NeuroSci 21:755–762

    Article  PubMed  Google Scholar 

  • Menard J, Treit D (1998) The septum and the hippocampus differentially mediate anxiolytic effects of R(+)-8-OH-DPAT. Behav Pharmacol 9:93–101

    PubMed  CAS  Google Scholar 

  • Meyer DK, Conzelmann U, Schultheiss K (1989) Effects of somatostatin-14 on the in vitro release of [H-3]GABA from slices of rat caudate putamen. Neuroscience 28:61–68

    Article  PubMed  CAS  Google Scholar 

  • Mitchell SN, Sharrott A, Cooper J, Greenslade RG (2000) Ventral subiculum administration of the somatostatin receptor agonist MK-678 increases dopamine levels in the nucleus accumbens. Eur J Pharmacol 395:43–46

    Article  PubMed  CAS  Google Scholar 

  • Moneta D, Richichi C, Aliprandi M, Dournoud P, Dutar P, Billard JM, Carlo AS, Viollet C, Hannon JP, Fehlmann D, Nunn C, Hoyer D, Epelbaum J, Vezzani A (2002) Somatostatin receptor subtypes 2 and 4 affect seizure susceptibility and hippocampal excitatory neurotransmission in mice. Eur J NeuroSci 16:843–849

    Article  PubMed  CAS  Google Scholar 

  • Morton CR, Hutchison WD, Hendry IA, Duggan AW (1989) Somatostatin—evidence for a role in thermal nociception. Brain Res 488:89–96

    Article  PubMed  CAS  Google Scholar 

  • Munozacedo G, Lopezsanudo S, Arilla E (1992) Reductions of Somatostatin receptors in rat hippocampus by treatment with 5, 7-dihydroxytryptamine. Neurosci Lett 146:60–64

    Article  CAS  Google Scholar 

  • Nilsson L, Mohammed AKH, Henriksson BG et al (1993) Environmental influence on somatostatin levels and gene expression in the rat-brain. Brain Res 628:93–98

    Article  PubMed  CAS  Google Scholar 

  • Obal F, Hajdu I, Gardi J, Szentirmai E, Krueger JM (2003) GHRH mediates somatostatin actions on sleep. Sleep 26:A18

    Google Scholar 

  • Pallis EG, Spyraki C, Thermos K (2006) Chronic antidepressant treatment modulates the release of somatostatin in the rat nucleus accumbens. Neurosci Lett 395:76–81

    Article  PubMed  CAS  Google Scholar 

  • Pallis EG, Antoniou K, Papadopoulou-Daifoti Z, Thermos K, Spyraki C (2007) Antidepressant-like activity of somatostatin using the forced swim test paradigm. Behav Pharmacol 18:S19

    Article  CAS  Google Scholar 

  • Pallis EG, Vasilaki A, Fehlmann D, Kastellakis A, Hoyer D, Spyraki C, Thermos K (2009) Antidepressants influence somatostatin levels and receptor pharmacology in brain. Neuropsychopharmacology 34:952–963

    Article  PubMed  CAS  Google Scholar 

  • Pawlikowski M, Melen-Mucha G (2003) Perspectives of new potential therapeutic applications of somatostatin analogs. Neuro Endocrinol Lett 24:21–27

    PubMed  CAS  Google Scholar 

  • Pellow S (1986) Anxiolytic and anxiogenic drug effects in a novel test of anxiety: are exploratory models of anxiety in rodents valid? Methods Find Exp Clin Pharmacol 8:557–565

    PubMed  CAS  Google Scholar 

  • Perez J, Vezzani A, Civenni G, Tutka P, Rizzi M, Schuepbach E, Hoyer D (1995) Functional effects of d-Phe-c[Cys-Tyr-d-Trp-Lys-Val-Cys]-Trp-NH2 and differential changes in somatostatin receptor messenger RNAs, binding sites and somatostatin release in kainic acid-treated rats. Neuroscience 65:1087–1097

    Article  PubMed  CAS  Google Scholar 

  • Pinel JPJ, Treit D, Rovner LI (1977) Temporal-lobe aggression in rats. Science 197:1088–1089

    Article  PubMed  CAS  Google Scholar 

  • Pinter E, Helyes Z, Szolcsanyi J (2006) Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 112:440–456

    Article  PubMed  CAS  Google Scholar 

  • Popova J, Ivanova E, Toshieva T, Iavorska N (1991) Growth-hormone and Somatostatin treatment change 5-HT1 receptor activity. Gen Pharmacol 22:1143–1146

    PubMed  CAS  Google Scholar 

  • Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391

    Article  PubMed  CAS  Google Scholar 

  • Porsolt RD, Lenegre A, McArthur RA (1991) Pharmacological models of depression. In: Oliver B, Mos J, Sanger JL (eds) Animal models in psychopharmacology. Birkhauser, Basel, pp 137–159

    Google Scholar 

  • Qiu C, Suzuki C, de Lecca L, Tallent MK (2004) Somatostatin receptor subtype 4 mediates the antiepileptic actions of somatostatin in hippocampus. Epilepsia 45:S23

    Article  Google Scholar 

  • Qiu C, Zeyda T, Johnson B, Hochgeschwender U, de Lecea L, Tallent MK (2008) Somatostatin receptor subtype 4 couples to the m-current to regulate seizures. J Neurosci 28:3567–3576

    Article  PubMed  CAS  Google Scholar 

  • Raynor K, Lucki I, Reisine T (1993) Somatostatin(1) receptors in the nucleus-accumbens selectively mediate the stimulatory effect of somatostatin on locomotor-activity in rats. J Pharmacol Exp Ther 265:67–73

    PubMed  CAS  Google Scholar 

  • Rohrer SP, Birzin ET, Mosley RT, Berk SC, Hutchins SM, Shen DM, Xiong YS, Hayes EC, Parmar RM, Foor F, Mitra SW, Degrado SJ, Shu M, Klopp JM, Cai SJ, Blake A, Chan WWS, Pasternak A, Yang LH, Patchett AA, Smith RG, Chapman KT, Schaeffer JM (1998) Rapid identification of subtype-selective agonists of the somatostatin receptor through combinatorial chemistry. Science 282:737–740

    Article  PubMed  CAS  Google Scholar 

  • Roosterman D, Stevens PA, Meyerhof W (1999) Different pathways of internalization of the somatostatin receptor sst3 and the possible autoreceptor sst1. Pediatr Res 45:559P2

    Article  Google Scholar 

  • Santis S, Kastellakis A, Kotzamani D, Pitarokoili K, Kokona D, Thermos K (2009) Somatostatin increases rat locomotor activity by activating sst(2) and sst(4) receptors in the striatum and via glutamatergic involvement. Naunyn-Schmiedeberg’s Arch Pharmacol 379:181–189

    Article  CAS  Google Scholar 

  • Santos NS, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65:1035–1041

    Article  PubMed  CAS  Google Scholar 

  • Schindler M, Holloway S, Hathway G, Woolf CJ, Humphrey PPA, Emson PC (1998) Identification of somatostatin sst(2(a)) receptor expressing neurones in central regions involved in nociception. Brain Res 798:25–35

    Article  PubMed  CAS  Google Scholar 

  • Schindler M, Humphrey PPA, Lohrke S et al (1999) Immunohistochemical localization of the somatostatin somatostatin(2(b)) receptor splice variant in the rat central nervous system. Neuroscience 90:859–874

    Article  PubMed  CAS  Google Scholar 

  • Selmer IS, Schindler M, Allen JP (2000) Advances in understanding neuronal somatostatin receptors. Regul Pept 90:1–18

    Article  PubMed  CAS  Google Scholar 

  • Steiger A, Guldner J, Hemmeter U, Rothe B, Wiedemann K, Holsboer F (1992) Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and nocturnal hormone-secretion in male controls. Neuroendocrinology 56:566–573

    Article  PubMed  CAS  Google Scholar 

  • Stragier B, Clinckers R, Meurs A, De Bundel D, Sarre S, Ebinger G, Michotte Y, Smolders I (2006) Involvement of the somatostatin-2 receptor in the anti-convulsant effect of angiotensin IV against pilocarpine-induced limbic seizures in rats. J Neurochem 98:1100–1113

    Article  PubMed  CAS  Google Scholar 

  • Tallent MK, Qiu C (2008) Somatostatin: an endogenous antiepileptic. Mol Cell Endocrinol 286:96–103

    Article  PubMed  CAS  Google Scholar 

  • Tallent MK, Siggins GR (1997) Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus. J Neurophysiol 78:3008–3018

    PubMed  CAS  Google Scholar 

  • Tallent MK, Siggins GR (1999) Somatostatin acts in CAI and CA3 to reduce hippocampal epileptiform activity. J Neurophysiol 81:1626–1635

    PubMed  CAS  Google Scholar 

  • Tashev R, Belcheva I (2008) Learning and memory effects of somatostatin microinjected into the rat dorsal neostriatum. Comptes Rendus de l’Academie Bulgare des Sciences 61:557–562

    CAS  Google Scholar 

  • Tashev R, Belcheva S, Milenov K et al (2001) Behavioral effects of somatostatin microinjected into caudate putamen. Neuropeptides 35:271–275

    Article  PubMed  CAS  Google Scholar 

  • Tashev R, Belcheva S, Belcheva I (2004) Differential effects of somatostatin on exploratory behavior after unilateral injections into rat neostriatum. Peptides 25:123–128

    Article  PubMed  CAS  Google Scholar 

  • Thermos K, Bagnoli P, Epelbaum J, Hoyer D (2006) The somatostatin sst(1) receptor: an autoreceptor for somatostatin in brain and retina? Pharmacol Ther 110:455–464

    Article  PubMed  CAS  Google Scholar 

  • Tokita K, Inoue T, Yamazaki S, Wang F, Yamaji T, Matsuoka N, Mutoh S (2005) FK962, a novel enhancer of somatostatin release, exerts cognitive-enhancing actions in rats. Eur J Pharmacol 527:111–120

    Article  PubMed  CAS  Google Scholar 

  • Toppila J, Niittymaki P, Porkka-Heiskanen T et al (2000) Intracerebroventricular and locus coeruleus microinjections of somatostatin antagonist decrease REM sleep in rats. Pharmacol Biochem Behav 66:721–727

    Article  PubMed  CAS  Google Scholar 

  • Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev 9:203–222

    Article  PubMed  CAS  Google Scholar 

  • Treit D, Pesold C, Rotzinger S (1993) Noninteractive effects of diazepam and amygdaloid lesions in two animal models of anxiety. Behav Neurosci 107:1099–1105

    Article  PubMed  CAS  Google Scholar 

  • Treit D, Degroot A, Shah A (2003) Animal models of anxiety and anxiolytic drug action. In: Kasper S, den Boer JA, Ad Sitsen JM (eds) Handbook of depression and anxiety, vol 2nd. New York, Marcel-Dekker

    Google Scholar 

  • van der Hoek J, Hofland LJ, Lamberts SWJ (2005) Novel subtype specific and universal somatostatin analogues: Clinical potential and pitfalls. Curr Pharm Des 11:1573–1592

    Article  PubMed  CAS  Google Scholar 

  • Vezzani A, Hoyer D (1999) Brain somatostatin: a candidate inhibitory role in seizures and epileptogenesis. Eur J NeuroSci 11:3767–3776

    Article  PubMed  CAS  Google Scholar 

  • Vezzani A, Serafini R, Ma S, Vigano G, Rizzi M, Samanin R (1991) A peptidase-resistant cyclic octapeptide analog of somatostatin (SMS-201–995) modulates seizures induced by quinolinic and kainic acids differently in the rat hippocampus. Neuropharmacology 30:345–352

    Article  PubMed  CAS  Google Scholar 

  • Viollet C, Vaillend C, Videau C, Bluet-Pajot MT, Ungerer A, L’Heritier A, Kopp C, Potier B, Billard JM, Schaeffer J, Smith RG, Rohrer SP, Wilkinson H, Zheng H, Epelbaum J (2000) Involvement of sst2 somatostatin receptor in locomotor, exploratory activity and emotional reactivity in mice. Eur J NeuroSci 12:3761–3770

    Article  PubMed  CAS  Google Scholar 

  • Xie Z, Sastry BR (1992) Actions of somatostatin on GABAergic synaptic transmission in the CA1 area of the hippocampus. Brain Res 591:239–247

    Article  PubMed  CAS  Google Scholar 

  • Walf AA, Frye CA (2008) Parity and estrogen-administration alter affective behavior of ovariectomized rats. Physiol Behav 93:351–356

    Article  PubMed  CAS  Google Scholar 

  • Weckbecker G, Lewis I, Albert R et al (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2:999–1017

    Article  PubMed  CAS  Google Scholar 

  • Willner P (1994) Animal models of depression. In: den Boer JA, Ad Sitsen JM (eds) Handbook of depression and anxiety. Marcel Dekker, New York, pp 291–316

    Google Scholar 

  • Wu TH, Lin CH (2008) IL-6 mediated alterations on immobile behavior of rats in the forced swim test via ERK1/2 activation in specific brain regions. Behav Brain Res 193:183–191

    Article  PubMed  CAS  Google Scholar 

  • Yamada Y, Post SR, Wang K et al (1992) Cloning and functional-characterization of a family of human and mouse somatostatin receptors expressed in brain, gastrointestinal-tract, and kidney. Proc Natl Acad Sci U S A 89:251–255

    Article  PubMed  CAS  Google Scholar 

  • Zeyda T, Diehl N, Paylor R, Brennan MB, Hochgeschwender U (2001) Impairment in motor learning of somatostatin null mutant mice. Brain Res 906:107–114

    Article  PubMed  CAS  Google Scholar 

  • Zhang K, Hamanaka K, Kitayama I, Soya H, Yoshizato H, Nakase S, Uesugi Y, Inui K, Nomura J, Okazaki Y (1999) Decreased expression of the mRNA for somatostatin in the periventricular nucleus of depression-model rats. Life Sci 65:PL87–PL94

    Article  PubMed  CAS  Google Scholar 

  • Ziegenbein M, Held K, Kuenzel HE, Murck H, Antonijevic IA, Steiger A (2004) The somatostatin analogue octreotide impairs sleep and decreases EEG sigma power in young male subjects. Neuropsychopharmacology 29:146–151

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgement

The research described in this paper was supported by a Natural Sciences and Engineering Research Council of Canada discovery grant awarded to DT.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dallas Treit.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Engin, E., Treit, D. Anxiolytic and antidepressant actions of somatostatin: the role of sst2 and sst3 receptors. Psychopharmacology 206, 281–289 (2009). https://doi.org/10.1007/s00213-009-1605-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-009-1605-5

Keywords

Navigation