Skip to main content

The Role of Peptides in Treatment of Psychiatric Disorders

  • Conference paper
Neuropsychopharmacology

Part of the book series: Journal of Neural Transmission. Supplementa ((NEURAL SUPPL,volume 64))

Abstract

About 25 years ago the observation that neuropeptides serve as signalling molecules in the nervous system generated great expectations for drug industry. In this article the progress made since then in exploiting neuropeptide systems pharmacologically in psychiatry is highlighted.

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

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arnauld E, Bibene V, Meynard J, Rodriguez F, Vincent JD (1989) Effects of chronic icv infusion of vasopressin on sleep-waking cycle of rats. Am J Physiol 256: R674–R684

    CAS  PubMed  Google Scholar 

  • Aström C, Lindholm J (1990) Growth hormone-deficient young adults have decreased deep sleep. Neuroendocrinology 51: 82–84

    Article  PubMed  Google Scholar 

  • Bardeleben von U, Holsboer F (1991) Effect of age upon the Cortisol response to human CRH in depressed patients pretreated with dexamethasone. Biol Psychiatry 29:1042–1050

    Article  Google Scholar 

  • Bardeleben von U, Holsboer F, Stalla GK, Müller OA (1985) Combined administration of human corticotropin-releasing factor and lysine vasopressin induces Cortisol escape from dexamethasone suppression in healthy subjects. Life Sci 37: 1613–1619

    Article  Google Scholar 

  • Binder EB, Kinkead B, Owens M J, Nemeroff CB (2001a) The role of neurotensin in the pathophysiology of schizophrenia and the mechanism of action of antipsychotic drugs. Biol Psychiatry 50: 856–872

    Article  CAS  PubMed  Google Scholar 

  • Binder EB, Kinkead B, Owens M J, Kilts CD, Nemeroff CB (2001b) Enhanced neurotensin neurotransmission is involved in the clinically relevant behavioral effects of antipsychotic drugs: evidence from animal models of sensorimotor gating. J Neurosci 21: 601–608

    CAS  PubMed  Google Scholar 

  • Binder EB, Gross RE, Nemeroff CB, Kilts CD (2002) Effects of neurotensin receptor antagonism on latent inhibition in Sprague-Dawley rats. Psychopharmacology 161: 288–295

    Article  CAS  PubMed  Google Scholar 

  • Born J, Kellner C, Uthgenannt D, Kern W, Fehm HL (1992) Vasopressin regulates human sleep by reducing rapid-eye-movement sleep. Am J Physiol 262: E295–E300

    CAS  PubMed  Google Scholar 

  • Bremner J, Narayan M, Anderson ER, Staib LH, Miller H, Charney DS (2000) Smaller hippocampal volume in major depression. Am J Psychiatry 157: 115–117

    Article  CAS  PubMed  Google Scholar 

  • Chang FC, Opp MR (1998) Blockade of corticotropin-releasing hormone receptors reduces spontaneous waking in the rat. Am J Physiol 275: R793–R802

    CAS  PubMed  Google Scholar 

  • Chang L, Karin M (2001) Mammalian MAP kinase signalling cascades. Nature 410: 37–40

    Article  CAS  PubMed  Google Scholar 

  • Chawla MK, Gutierrez GM, Young WS, McMullen NT, Ranee NE (1997) Localization of neurons expressing substance P and neurokinin B gene transcripts in the human hypothalamus and basal forebrain. J Comp Neurol 384:429–442

    Article  CAS  PubMed  Google Scholar 

  • Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50: 260–265

    Article  CAS  PubMed  Google Scholar 

  • Conti AC, Cryan JF, Dalvi A, Lucki I, Blendy JA (2002) cAMP response element-binding protein is essential for the upregulation of brain-derived neurotrophic factor transcription, but not the behavioral or endocrine responses to antidepressant drugs. J Neurosci 22: 3262–3268

    CAS  PubMed  Google Scholar 

  • Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci 98: 12796–12801

    Article  CAS  PubMed  Google Scholar 

  • De Wied D (1993) From stress hormones to neuropeptides. In: Burbach JPH, de Wied D (eds) Brain functions of neuropeptides. A current view. The Parthenon Publishing Group, New York, pp 65–84

    Google Scholar 

  • Dinan TG, Lavelle E, Scott L, Newell-Price J, Medbak S, Grossman AB (1999) Desmopressin normalizes the blunted adrenocorticotropin response to corticotropin-releasing hormone in melancholic depression: evidence of enhanced vasopressinergic responsitivity. J Clin Endocrinol Metab 84: 2238–2240

    Article  CAS  PubMed  Google Scholar 

  • Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN (2001) Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 77: 916–928

    Article  CAS  PubMed  Google Scholar 

  • Ehlers CL, Kupfer DJ (1987) Hypothalamic peptide modulation of EEG sleep in depression: a further application of the S-process hypothesis. Biol Psychiatry 22: 513— 517

    Article  PubMed  Google Scholar 

  • Ehlers CL, Reed TK, Henriksen SJ (1986) Effects of corticotropin-releasing factor and growth hormone-releasing factor on sleep and activity in rats. Neuroendocrinology 42: 467–474

    Article  CAS  PubMed  Google Scholar 

  • File SE (2000) NKP608, an NK1 receptor antagonist, has an anxiolytic action in the social interaction test in rats. Psychopharmacology 152: 105–109

    Article  CAS  PubMed  Google Scholar 

  • Freedman R, Waldo M, Bickford-Wimer P, Nagamoto H (2001) Elementary neuronal dysfunctions in schizophrenia. Schizophr Res 4: 233–243

    Article  Google Scholar 

  • Frieboes RM, Murck H, Schier T, Holsboer F, Steiger A (1997) Somatostatin impairs sleep in elderly human subjects. Neuropsychopharmacology 16: 339–345

    Article  CAS  PubMed  Google Scholar 

  • Gonzales MM, Valatx JL (1998) Involvement of stress in the sleep rebound mechanism induced by sleep deprivation in the rat: use of alpha-helical CRH (9–41). Behav Pharmacol 9: 655–662

    Article  Google Scholar 

  • Gould E, McEwen BS, Tanapat P, Galea LAM, Fuchs E (1997) Neurogenesis in the dentate gyrus of the adult tree shrew is regulated by psychosocial stress and NMD A receptor activation. J Neurosci 17: 2492–2498

    CAS  PubMed  Google Scholar 

  • Griebel G, Simiand J, Serradeil-LeGal C, Wagnon J, Pascal M, Scatton B, Maffrand JP, Soubrie P (2002) Anxiolytic-and antidepressant-like effects of the non-peptide vasopressin Vlb receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders. Proc Natl Acad Sci Early Edition: 1–6

    Google Scholar 

  • Gulyas J, Rivier C, Perrin M, Koerber SC, Sutton S, Corrigan A et al. (1995) Potent, structurally constrained agonists and competitive antagonists of corticotropin-releasing factor. Proc Natl Acad Sci 92: 10575–10579

    Article  CAS  PubMed  Google Scholar 

  • Heuser I, Bissette G, Dettling M, Schweiger U, Gotthardt U, Schmider J, Lammers CH, Nemeroff CB, Holsboer F (1998) Cerebrospinal fluid concentrations of corticotropin-releasing hormone, vasopressin, and somatostatin in depressed patients and healthy controls: response to amitriptyline treatment. Depression & Anxiety 8: 71–79

    Article  CAS  PubMed  Google Scholar 

  • Hökfelt T (1991) Neuropeptides in perspective: the last ten years. Neuron 7: 867–879

    Article  PubMed  Google Scholar 

  • Holsboer F (1999) The rationale for corticotropin-releasing hormone receptor (CRH-R) antagonists to treat depression and anxiety. J Psychiatr Res 33: 181–214

    Article  CAS  PubMed  Google Scholar 

  • Holsboer F (2000) The Cortisol receptor hypothesis of depression. Neuropsychopharmacology 23: 477–501

    Article  CAS  PubMed  Google Scholar 

  • Holsboer F (2001) Antidepressant drug discovery in the postgenomic era. World J Biol Psychiatry 2: 165–177

    Article  CAS  PubMed  Google Scholar 

  • Holsboer F, Barden N (1996) Antidepressants and HPA regulation. Endcr Rev 17: 187–205

    Article  CAS  Google Scholar 

  • Holsboer F, von Bardeleben U, Steiger A (1988) Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man. Neuroendocrinology 48: 32–38

    Article  CAS  PubMed  Google Scholar 

  • Horvath TL, Diano S, Sotonyi P, Heiman M, Tschöp M (2001) Ghrelin and the regulation of energy balance — a hypothalamic perspective. Endocrinology 142: 4163–4169

    CAS  PubMed  Google Scholar 

  • Hsu SY, Hsueh AJW (2001) Human stresscopin and stresscopin-related peptide are selective ligangs for the type 2 corticotropin-releasing hormone receptor. Nat Med 7: 605–611

    Article  CAS  PubMed  Google Scholar 

  • Keck ME, Holsboer F (2001) Hyperactivity of CRH neuronal circuits as a target for therapeutic interventions in affective disorders. Peptides 22: 835–844

    Article  CAS  PubMed  Google Scholar 

  • Keck ME, Welt T, Wigger A, Renner U, Engelmann M, Holsboer F, Landgraf R (2001a) The anxiolytic effect of the CRH1 receptor antagonist R121919 depends on innate emotionality in rats. Eur J Neurosci 13: 373–380

    Article  CAS  PubMed  Google Scholar 

  • Keck ME, Wigger A, Welt T, Müller MB, Gesing A, Reul JMHM, Holsboer F, Landgraf R, Neumann ID (2001b) Vasopressin mediates the response of the combined dexamethasone/CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders. Neuropsychopharmacology 26: 94–105

    Article  Google Scholar 

  • Korte M, Carroll P, Wolf E, Brem G, Thoenen H, Bonhoeffer T (1995) Hippocampal long-term potentiation is impaired in mice lacking brain-derived neurotrophic factor. Proc Natl Acad Sci USA 92: 8.856–8.860

    Article  Google Scholar 

  • Kovalchuk Y, Hanse E, Kafitz KW, Konnerth A (2002) Postsynaptic induction of BDNF-mediated long-term potentiation. Science 295: 1729–1734

    Article  CAS  PubMed  Google Scholar 

  • Kramer MS, Cutler N, Feighner J, Shrivastava R, Carman J et al. (1998) Distinct mechanism for antidepressant activity by blockade of central substance P receptors. Science 281: 1640–1645

    Article  CAS  PubMed  Google Scholar 

  • Krieger DT (1983) Brain peptides: what, where and why? Science 222: 975–985

    Article  CAS  PubMed  Google Scholar 

  • Lancel M, Müller-Preuss P, Wigger A, Landgraf R, Holsboer F (2002) The CRH1 receptor antagonist R121919 attenuates stress-elicited sleep disturbances in rats, particularly in those with high innate anxiety. J Psychiatr Res 36: 197–208

    Article  PubMed  Google Scholar 

  • Landgraf R (2001) Neuropeptides and anxiety-related behavior. Endocr J 48: 517— 533

    Google Scholar 

  • Landgraf R, Gerstberger R, Montkowski A, Probst JC, Wotjak CT, Holsboer F, Engelmann M (1995) VI vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats. J Neurosci 15: 4250–4258

    CAS  PubMed  Google Scholar 

  • Liebsch G, Montkowski A, Holsboer F, Landgraf R (1998) Behavioral profiles of two Wistar rat lines selectively bred for high or low anxiety-related behavior. Behav Brain Res 94: 301–310

    Article  CAS  PubMed  Google Scholar 

  • Linthorst ACE, Flachskamm C, Müller-Preuss P, Holsboer F, Reul JMHM (1995) Effect of bacterial endotoxin and interleukin-lß on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study. J Neurosci 15: 2920–2934

    CAS  PubMed  Google Scholar 

  • Lucassen PJ, Müller MB, Holsboer F, Bauer J, Holtrop A, Wouda J, WJG Hoogendijk, De Kloet ER, Swaab DF (2001) Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure. Am J Pathol 158: 453–468

    Article  CAS  PubMed  Google Scholar 

  • Montkowski A, Holsboer F (1997) Intact spatial learning and memory in transgenic mice with reduced BDNE. Neuroreport 8: 779–782

    Article  CAS  PubMed  Google Scholar 

  • Müller MB, Lucassen P, Yassouridis A, Hoogendijk WGJ, Holsboer F, Swaab DF (2001) Neither major depression nor glucocorticoid treatment affects the cellular integrity of the human hippocampus. Eur J Neurosci 14: 1603–1612

    Article  PubMed  Google Scholar 

  • Müller MB, Preil J, Renner U, Zimmermann S, Kresse AE, Stalla GK, Keck ME, Holsboer F, Wurst W (2001) Expression of CRHR1 and CRHR2 in mouse pituitary and adrenal gland: implications for HPA system regulation. Endocrinology 142: 4150–4153

    Article  PubMed  Google Scholar 

  • Nibuya M, Takahashi M, Rüssel DS, Duman RS (1999) Chronic stress increases catalytic TrB mRNA in rat hippocampus. Neurosci Lett 267: 81–84

    Article  CAS  PubMed  Google Scholar 

  • Penalva RG, Flachskamm C, Zimmermann S, Wurst W, Holsboer F, Reul JMHM, Linthorst ACE (2002) Corticotropin-releasing hormone receptor type 1-deficiency enhances hippocampal serotonergic neurotransmission: an in vivo microdialysis study in mutant mice. Neuroscience 109: 253–266

    Article  CAS  PubMed  Google Scholar 

  • Perras B, Pannenborg H, Marshall L, Pietrowsky R, Born J, Fehm HL (1997) Three months of intranasal vasopressin increased sleep time, slow wave sleep and REM sleep in healthy old humans. Exp Clin Endocrinol Diabetes [Suppl] 1: 23

    Google Scholar 

  • Preil J, Müller MB, Gesing A, Reul JMHM, Sillaber I, Gaalen M, Landgrebe J, Stenzel-Poore M, Holsboer F, Wurst W (2001) Regulation of the hypothalamic-pituitary-adrenocortical system in mice deficient for corticotropin-releasing hormone receptor 1 and 2. Endocrinology 142: 4946–4955

    Article  CAS  PubMed  Google Scholar 

  • Purba JS, Hoogendijk WJG, Hofman MA, Swaab DF (1996) Increased number of vasopressin-and oxytocin-expressing neurons in the paraventricular nucleus of the hypothalamus in depression. Arch Gen Psychiatry 53: 137–143

    Article  CAS  PubMed  Google Scholar 

  • Raadsheer FC, Hoogendijk WJG, Stam FC, Tilders FHJ, Swaab DF (1994) Increased numbers of corticotropin-releasing hormone expressing neurons in the hypothalamic paraventricular nucleus of depressed patients. Neuroendocrinology 60: 433–436

    Article  Google Scholar 

  • Reul JMHM, Holsboer F (2002) Corticotropin-releasing factor receptors 1 and 2 in anxiety and depression. Curr Opin Pharmacol 2: 23–33

    Article  CAS  PubMed  Google Scholar 

  • Santarelli L, Gobbi G, Debs PC, Sibille EL, Blier P, Hen R, Heath MJS (2001) Genetic and pharmacological disruption of neurokinin 1 receptor function decreases anxiety-related behaviors and increases serotonergic function. Proc Natl Acad Sci USA 98: 1912–1917

    Article  CAS  PubMed  Google Scholar 

  • Schwarze SR, Hruska KA, Dowdy SF (2000) Protein transduction: unrestricted delivery into all cells? Trends Cell Biol 10: 290–295

    Article  CAS  PubMed  Google Scholar 

  • Sheline Y, Wany P, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93: 3908–3913

    Article  CAS  PubMed  Google Scholar 

  • Sheline Y, Sanghavi M, Mintun MA, Gado MH (1999) Depression duration but not age predicts hippocampal volume loss in medically healthy women with recurrent major depression. J Neurosci 19: 5034–5043

    CAS  PubMed  Google Scholar 

  • Shirayama Y, Chen ACH, Nakagawa S, Rüssel DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22: 3251–3261

    CAS  PubMed  Google Scholar 

  • Sillaber I, Rammes G, Zimmermann S, Mahal B, Zieglgänsberger W, Wurst W, Holsboer F, Spanagel R (2002) Enhanced and delayed stress-induced alcohol drinking in mice lacking functional CRH1 receptors. Science 296: 931–933

    Article  CAS  PubMed  Google Scholar 

  • Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress alters the express of brain-derived neurotrophic factor and neurotrophin-3 mR-NAs in the hippocampus. J Neurosci 15: 1768–1777

    CAS  PubMed  Google Scholar 

  • Spengler D, Rupprecht R, Phi Van L, Holsboer F (1992) Identification and characterization of a 3’,5’-cyclic adenosine monophosphate-responsive element in the human corticotropin-releasing hormone gene promoter. Mol Endocrinol 6: 1931–1941

    CAS  PubMed  Google Scholar 

  • Steiger A, Holsboer F (1997) Neuropeptides and human sleep. Sleep 20: 1038–1052

    CAS  PubMed  Google Scholar 

  • Steiger A, Herth T, Holsboer F (1987) Sleep-electroencephalography and the secretion of Cortisol and growth hormone in normal controls. Acta Endocrinol (Copenh) 116: 36–42

    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  CAS  PubMed  Google Scholar 

  • Swerdlow NR, Geyer MA (1998) Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr Bull 24: 285–301

    Article  CAS  PubMed  Google Scholar 

  • Swerdlow NR, Braff DL, Geyer MA (1999) Cross-species studies of sensorimotor gating of the startle reflex. Ann NY Acad Sci 877: 202–216

    Article  CAS  PubMed  Google Scholar 

  • Teixeira RM, Santos AR, Ribeiro SJ, Calixto JB, Rae GA, De Lima TC (1996) Effects of central administration of tachykinin receptor agonists and antagonists on plus-maze behavior in mice. Eur J Pharmacol 311: 7–14

    Article  CAS  PubMed  Google Scholar 

  • Thome J, Sakai N, Shin K, Steffen C, Zhang YJ, Impey S, Storm D, Duman RS (2000) Cyclic AMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 20: 4030–4036

    CAS  PubMed  Google Scholar 

  • Timpl P, Spanagel R, Sillaber I, Kresse A, Reul JMHM, Stalla GK, Blanquet V, Steckler T, Holsboer F, Wurst W (1998) Impaired stress response adn reduced anxiety in mice lacking a functional corticotropin-releasing hormone receptor 1. Nat Genet 19: 162–166

    Article  CAS  PubMed  Google Scholar 

  • Tsuchiyama Y, Uchimura N, Sakamoto T, Maeda H, Kotorii T (1995) Effects of hCRH on sleep and body temperature rhythms. Psychiatry Clin Neurosci 49: 299–304

    Article  CAS  PubMed  Google Scholar 

  • Zobel AW, Nickel T, Künzel HE, Ackl N, Sonntag A, Ising M, Holsboer F (2000) Effects of the high-affinity corticotropin-releasing hormone receptor 1 antagonist R121919 in major depression: the first 20 patients treated. J Psychiatr Res 34: 171–181

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag/Wien

About this paper

Cite this paper

Holsboer, F. (2003). The Role of Peptides in Treatment of Psychiatric Disorders. In: Neuropsychopharmacology. Journal of Neural Transmission. Supplementa, vol 64. Springer, Vienna. https://doi.org/10.1007/978-3-7091-6020-6_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-6020-6_2

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-211-83903-4

  • Online ISBN: 978-3-7091-6020-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics