Psychopharmacology

, Volume 206, Issue 2, pp 281–289

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

Original Investigation
  • 243 Downloads

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.

Keywords

Somatostatin Anxiety Depression Agonist Plus-maze Swim test 

References

  1. Baraban SC, Tallent MK (2004) Interneuron diversity series: interneuronal neuropeptides—endogenous regulators of neuronal excitability. Trends Neurosci 27:135–142PubMedCrossRefGoogle Scholar
  2. 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–R1491Google Scholar
  3. 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 269:7–14PubMedGoogle Scholar
  4. Binaschi A, Bregola G, Simonato M (2003) On the role of somatostatin in seizure control: clues from the hippocampus. Rev Neurosci 14:285–301PubMedGoogle Scholar
  5. 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 179:77–79PubMedCrossRefGoogle Scholar
  6. Breder CD, Yamada Y, Yasuda K, Seino S, Saper CB, Bell GI (1992) Differential expression of somatostatin receptor subtypes in brain. J Neurosci 12:3920–3934PubMedGoogle Scholar
  7. Buckmaster PS, Otero-Corchon V, Rubinstein M, Low MJ (2002) Heightened seizure severity in somatostatin knockout mice. Epilepsy Res 48:43–56PubMedCrossRefGoogle Scholar
  8. Carlton SM, Du JH, Zhou ST, Coggeshall RE (2001) Tonic control of peripheral cutaneous nociceptors by somatostatin receptors. J Neurosci 21:4042–4049PubMedGoogle Scholar
  9. 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 110:616–627PubMedCrossRefGoogle Scholar
  10. Cervia D, Casini G, Bagnoli P (2008) Physiology and pathology of somatostatin in the mammalian retina: a current view. Mol Cell Endocrinol 286:112–122PubMedCrossRefGoogle Scholar
  11. Chesselet MD, Reisine T (1983) Somatostatin regulates dopamine release in rat striatal slices and cat caudate nuclei. J Neurosci 3:232–236PubMedGoogle Scholar
  12. Chrubasik S, Ziegler R (1996) Does the somatostatin analogue pctreotide have a role in pain relief? Pain Clin 8:369–375Google Scholar
  13. Danguir J (1986) Intracerebroventricular infusion of somatostatin selectively increases paradoxical sleep in rats. Brain Res 367:26–30PubMedCrossRefGoogle Scholar
  14. 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 43:356–366Google Scholar
  15. Detke M, Rickels M, Lucki I (1995) Active behaviors in the rat forced swimming test differentially activated by serotonergic and noradrenergic antidepressants. Psychopharmacology 121:66–72PubMedCrossRefGoogle Scholar
  16. 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 8:476–485PubMedCrossRefGoogle Scholar
  17. 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 1–43Google Scholar
  18. 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 112:455–466PubMedCrossRefGoogle Scholar
  19. Dyer K, Cain DP (2007) Water maze impairments after combined depletion of somatostatin and serotonin in the rat. Behav Brain Res 181:85–95PubMedCrossRefGoogle Scholar
  20. Engin E, Treit D (2008a) Dissociation of the anxiolytic-like effects of Avpr1a and Avpr1b receptor antagonists in the dorsal and ventral hippocampus. Neuropeptides 42:411–421PubMedCrossRefGoogle Scholar
  21. 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 32:1399–1419CrossRefGoogle Scholar
  22. Engin E, Stellbrink J, Treit D et al (2008) Anxiolytic and antidepressant effects of intracerebroventricularly administered somatostatin: behavioral and neurophysiological evidence. Neuroscience 157:666–676PubMedCrossRefGoogle Scholar
  23. Engin E, Treit D, Dickson CT (2009) Anxiolytic- and antidepressant-like properties of ketamine in behavioral and neurophysiological animal models. Neuroscience 161(2):359–369PubMedCrossRefGoogle Scholar
  24. 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 64:339–355PubMedCrossRefGoogle Scholar
  25. 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 16:3097–3103PubMedGoogle Scholar
  26. Frieboes RM, Murck H, Shier T et al (1997) Somatostatin impairs sleep in elderly human subjects. Neuropsychopharmacology 16:339–345PubMedCrossRefGoogle Scholar
  27. Gastambide F, Viollet C, Lepousez G, Epelbaum J, Guillou JL (2009) Hippocampal somatostatinR4 somatostatin receptors control the selection of memory strategies. Psychopharmacology 202:153–163PubMedCrossRefGoogle Scholar
  28. Gheorvassaki EG, Thermos K, Liapakis G, Spyraki C (1992) Effects of acute and chronic desipramine treatment on somatostatin receptors in brain. Psychopharmacology 108:363–366PubMedCrossRefGoogle Scholar
  29. 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 994:115–123PubMedCrossRefGoogle Scholar
  30. 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 89:909–926PubMedCrossRefGoogle Scholar
  31. Hathway GJ, Humphrey PPA, Kendrick KM (2004) Somatostatin induces striatal dopamine release and contralateral turning behaviour in the mouse. Neurosci Lett 358:127–131PubMedCrossRefGoogle Scholar
  32. Hervieu G, Emson PC (1999) Visualisation of somatostatin receptor sst3 in the rat central nervous system. Mol Brain Res 71:290–303PubMedCrossRefGoogle Scholar
  33. 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 131:571–577PubMedCrossRefGoogle Scholar
  34. Hogg S (1996) A review of the validity and variability of the elevated plus-maze as an animal model of anxiety. Pharmacol Biochem Behav 54:21–30PubMedCrossRefGoogle Scholar
  35. 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 35:1109–1120PubMedCrossRefGoogle Scholar
  36. 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 31:46–56PubMedCrossRefGoogle Scholar
  37. 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 47:97–107PubMedCrossRefGoogle Scholar
  38. 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 761:127–134PubMedCrossRefGoogle Scholar
  39. 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 15:252–260CrossRefGoogle Scholar
  40. 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 59:175–184PubMedCrossRefGoogle Scholar
  41. Korte M, De Boer SF (2003) A robust animal model of state anxiety: fear-potentiated behaviour in the elevated plus-maze. Eur J Pharmacol 463:163–175PubMedCrossRefGoogle Scholar
  42. 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 14:567–570PubMedCrossRefGoogle Scholar
  43. 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 84:1464–1474PubMedGoogle Scholar
  44. 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 13:277–282CrossRefGoogle Scholar
  45. Low MJ, Juarez R, Rubinstein M, Carey K (1998) Impaired learning and memory in somatostatin-deficient mice. Brain Res 809:P311Google Scholar
  46. Marazioti A, Kastellakis A, Antoniou K, Papasava D, Thermos K (2005) Somatostatin receptors in the ventral pallidum/substantia innominata modulate rat locomotor activity. Psychopharmacology 181:319–326PubMedCrossRefGoogle Scholar
  47. 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:S428Google Scholar
  48. 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 201:413–422PubMedCrossRefGoogle Scholar
  49. 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 642:11–19PubMedCrossRefGoogle Scholar
  50. Matsuoka N, Yamazaki M, Yamaguchi I (1995) Changes in brain somatostatin in memory-deficient rats: comparison with cholinergic markers. Neuroscience 66:617–626PubMedCrossRefGoogle Scholar
  51. Mazarati AM, Telegdy G (1992) Effects of somatostatin and antisomatostatin serum on picrotoxin-kindled seizures. Neuropharmacology 31:793–797PubMedCrossRefGoogle Scholar
  52. McDonald AJ, Mascagni F (2002) Immunohistochemical characterization of somatostatin containing interneurons in the rat basolateral amygdala. Brain Res 943:237–244PubMedCrossRefGoogle Scholar
  53. McEown K, Treit D (2009) The role of the dorsal and ventral hippocampus in fear and memory of a shock-probe experience. Brain Res 1251:185–194PubMedCrossRefGoogle Scholar
  54. 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 18:329–346PubMedCrossRefGoogle Scholar
  55. Meis S, Sosulina L, Schulz S et al (2005) Mechanisms of somatostatin-evoked responses in neurons of the rat lateral amygdala. Eur J NeuroSci 21:755–762PubMedCrossRefGoogle Scholar
  56. Menard J, Treit D (1998) The septum and the hippocampus differentially mediate anxiolytic effects of R(+)-8-OH-DPAT. Behav Pharmacol 9:93–101PubMedGoogle Scholar
  57. 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 28:61–68PubMedCrossRefGoogle Scholar
  58. 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 395:43–46PubMedCrossRefGoogle Scholar
  59. 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 16:843–849PubMedCrossRefGoogle Scholar
  60. Morton CR, Hutchison WD, Hendry IA, Duggan AW (1989) Somatostatin—evidence for a role in thermal nociception. Brain Res 488:89–96PubMedCrossRefGoogle Scholar
  61. Munozacedo G, Lopezsanudo S, Arilla E (1992) Reductions of Somatostatin receptors in rat hippocampus by treatment with 5, 7-dihydroxytryptamine. Neurosci Lett 146:60–64CrossRefGoogle Scholar
  62. Nilsson L, Mohammed AKH, Henriksson BG et al (1993) Environmental influence on somatostatin levels and gene expression in the rat-brain. Brain Res 628:93–98PubMedCrossRefGoogle Scholar
  63. Obal F, Hajdu I, Gardi J, Szentirmai E, Krueger JM (2003) GHRH mediates somatostatin actions on sleep. Sleep 26:A18Google Scholar
  64. Pallis EG, Spyraki C, Thermos K (2006) Chronic antidepressant treatment modulates the release of somatostatin in the rat nucleus accumbens. Neurosci Lett 395:76–81PubMedCrossRefGoogle Scholar
  65. 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:S19CrossRefGoogle Scholar
  66. 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 34:952–963PubMedCrossRefGoogle Scholar
  67. Pawlikowski M, Melen-Mucha G (2003) Perspectives of new potential therapeutic applications of somatostatin analogs. Neuro Endocrinol Lett 24:21–27PubMedGoogle Scholar
  68. 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 8:557–565PubMedGoogle Scholar
  69. 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 65:1087–1097PubMedCrossRefGoogle Scholar
  70. Pinel JPJ, Treit D, Rovner LI (1977) Temporal-lobe aggression in rats. Science 197:1088–1089PubMedCrossRefGoogle Scholar
  71. Pinter E, Helyes Z, Szolcsanyi J (2006) Inhibitory effect of somatostatin on inflammation and nociception. Pharmacol Ther 112:440–456PubMedCrossRefGoogle Scholar
  72. Popova J, Ivanova E, Toshieva T, Iavorska N (1991) Growth-hormone and Somatostatin treatment change 5-HT1 receptor activity. Gen Pharmacol 22:1143–1146PubMedGoogle Scholar
  73. Porsolt RD, Anton G, Blavet N, Jalfre M (1978) Behavioral despair in rats: a new model sensitive to antidepressant treatments. Eur J Pharmacol 47:379–391PubMedCrossRefGoogle Scholar
  74. 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 137–159Google Scholar
  75. Qiu C, Suzuki C, de Lecca L, Tallent MK (2004) Somatostatin receptor subtype 4 mediates the antiepileptic actions of somatostatin in hippocampus. Epilepsia 45:S23CrossRefGoogle Scholar
  76. 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 28:3567–3576PubMedCrossRefGoogle Scholar
  77. 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 265:67–73PubMedGoogle Scholar
  78. 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 282:737–740PubMedCrossRefGoogle Scholar
  79. Roosterman D, Stevens PA, Meyerhof W (1999) Different pathways of internalization of the somatostatin receptor sst3 and the possible autoreceptor sst1. Pediatr Res 45:559P2CrossRefGoogle Scholar
  80. 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 379:181–189CrossRefGoogle Scholar
  81. Santos NS, Figueira-Coelho J, Martins-Silva J, Saldanha C (2003) Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 65:1035–1041PubMedCrossRefGoogle Scholar
  82. 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 798:25–35PubMedCrossRefGoogle Scholar
  83. 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 90:859–874PubMedCrossRefGoogle Scholar
  84. Selmer IS, Schindler M, Allen JP (2000) Advances in understanding neuronal somatostatin receptors. Regul Pept 90:1–18PubMedCrossRefGoogle Scholar
  85. 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 56:566–573PubMedCrossRefGoogle Scholar
  86. 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 98:1100–1113PubMedCrossRefGoogle Scholar
  87. Tallent MK, Qiu C (2008) Somatostatin: an endogenous antiepileptic. Mol Cell Endocrinol 286:96–103PubMedCrossRefGoogle Scholar
  88. Tallent MK, Siggins GR (1997) Somatostatin depresses excitatory but not inhibitory neurotransmission in rat CA1 hippocampus. J Neurophysiol 78:3008–3018PubMedGoogle Scholar
  89. Tallent MK, Siggins GR (1999) Somatostatin acts in CAI and CA3 to reduce hippocampal epileptiform activity. J Neurophysiol 81:1626–1635PubMedGoogle Scholar
  90. 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 61:557–562Google Scholar
  91. Tashev R, Belcheva S, Milenov K et al (2001) Behavioral effects of somatostatin microinjected into caudate putamen. Neuropeptides 35:271–275PubMedCrossRefGoogle Scholar
  92. Tashev R, Belcheva S, Belcheva I (2004) Differential effects of somatostatin on exploratory behavior after unilateral injections into rat neostriatum. Peptides 25:123–128PubMedCrossRefGoogle Scholar
  93. Thermos K, Bagnoli P, Epelbaum J, Hoyer D (2006) The somatostatin sst(1) receptor: an autoreceptor for somatostatin in brain and retina? Pharmacol Ther 110:455–464PubMedCrossRefGoogle Scholar
  94. 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 527:111–120PubMedCrossRefGoogle Scholar
  95. 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 66:721–727PubMedCrossRefGoogle Scholar
  96. Treit D (1985) Animal models for the study of anti-anxiety agents: a review. Neurosci Biobehav Rev 9:203–222PubMedCrossRefGoogle Scholar
  97. Treit D, Pesold C, Rotzinger S (1993) Noninteractive effects of diazepam and amygdaloid lesions in two animal models of anxiety. Behav Neurosci 107:1099–1105PubMedCrossRefGoogle Scholar
  98. 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-DekkerGoogle Scholar
  99. van der Hoek J, Hofland LJ, Lamberts SWJ (2005) Novel subtype specific and universal somatostatin analogues: Clinical potential and pitfalls. Curr Pharm Des 11:1573–1592PubMedCrossRefGoogle Scholar
  100. Vezzani A, Hoyer D (1999) Brain somatostatin: a candidate inhibitory role in seizures and epileptogenesis. Eur J NeuroSci 11:3767–3776PubMedCrossRefGoogle Scholar
  101. 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 30:345–352PubMedCrossRefGoogle Scholar
  102. 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 12:3761–3770PubMedCrossRefGoogle Scholar
  103. Xie Z, Sastry BR (1992) Actions of somatostatin on GABAergic synaptic transmission in the CA1 area of the hippocampus. Brain Res 591:239–247PubMedCrossRefGoogle Scholar
  104. Walf AA, Frye CA (2008) Parity and estrogen-administration alter affective behavior of ovariectomized rats. Physiol Behav 93:351–356PubMedCrossRefGoogle Scholar
  105. Weckbecker G, Lewis I, Albert R et al (2003) Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2:999–1017PubMedCrossRefGoogle Scholar
  106. 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 291–316Google Scholar
  107. 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 193:183–191PubMedCrossRefGoogle Scholar
  108. 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 89:251–255PubMedCrossRefGoogle Scholar
  109. Zeyda T, Diehl N, Paylor R, Brennan MB, Hochgeschwender U (2001) Impairment in motor learning of somatostatin null mutant mice. Brain Res 906:107–114PubMedCrossRefGoogle Scholar
  110. 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–PL94PubMedCrossRefGoogle Scholar
  111. 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 29:146–151PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of AlbertaEdmontonCanada
  2. 2.Centre for NeuroscienceUniversity of AlbertaEdmontonCanada

Personalised recommendations