Cited by 127Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyStress Responses and Cortisol

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The Involvement of the Vasopressin System in Stress-Related Disorders

Landgraf, Rainer·2006·CNS & Neurological Disorders - Drug Targets

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Abstract

The neuropeptide arginine vasopressin (AVP) is released within distinct brain areas upon appropriate stimulation, including stressful challenges. Following its predominantly dendritic release, AVP triggers a variety of receptor-mediated effects related to behavioral and neuroendocrine regulation. Antagonist treatment together with other sophisticated loss-of-function and gain-of-function approaches provide evidence for a multiple involvement of V1a and V1b receptor subtypes in stress-related behavior and disorders, including anxiety disorders, comorbid depression and their neuroendocrine concomitants. Conversely, in the high versus low anxiety (HAB/LAB) rat model, the phenotype of extreme trait anxiety is associated with a polymorphism-driven overexpression of AVP in the hypothalamic paraventricular nucleus. This overexpression of AVP might be considered a final common pathway of anxiety-related behavior. The capability of both responding to stressful stimuli and mediating genetic polymorphisms makes the central release of AVP a key process for converging (i.e., environmentally and genetically driven) behavioral regulation. Polymorphisms in the promoter structures of the AVP gene and AVP receptor genes, underlying differences in gene expression, thus contribute to individual variation in behavior as well as to psychopathology, making genes of the brain AVP system and their products a promising target for therapeutic interventions.

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Background
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Further genetic evidence implicates the vasopressin system in childhood‐onset mood disorders
Dempster, E. L., Burcescu, I., Wigg, K. G., Kiss, E., Baji, I., Gádoros, J., Tamás, Z., Kapornai, K., Daróczy, G., Kennedy, J. L., et al. (2009) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2009.06930.x · Cited by 28
“There is considerable support from both animal and human studies for a role for the AVP system in the aetiology of depressive symptoms (Alescio-Lautier et al., 2000; Zhou et al., 2001; Landgraf, 2006; Veenema et al., 2006).”
BackgroundResultInfluential
Design and Synthesis of the First Selective Agonists for the Rat Vasopressin V 1b Receptor: Based on Modifications of Deamino-[Cys]arginine Vasopressin at Positions 4 and 8
Peña, A., Murat, B., Trueba, M., Ventura, M. A., Wo, N. C., Szeto, H. H., Cheng, L., Stoev, S. B., Guillon, G., & Manning, M. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm060928n · Cited by 33
Interaction of AT1 receptors and V1a receptors-mediated effects in the central cardiovascular control during the post-infarct state
Cudnoch‐Jędrzejewska, A., Dobruch, J. T., Puchalska, L., & Szczepanska‐Sadowska, E. K. (2007) · Regulatory Peptides · doi:10.1016/j.regpep.2007.01.010 · Cited by 26
MDMA ('Ecstasy'), oxytocin and vasopressin modulate social preference in rats: a role for handling and oxytocin receptors
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Distribution of the Vasotocin Subtype Four Receptor ( VT 4 R ) in the Anterior Pituitary Gland of the Chicken, G allus gallus, and its Possible Role in the Avian Stress Response
Selvam, R., Jurkevich, A., Kang, S. W., Mikhailova, M. V., Cornett, L. E., & Kuenzel, W. J. (2012) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2012.02370.x · Cited by 25
Lithium monotherapy increases ACTH and cortisol response in the DEX/CRH test in unipolar depressed subjects. A study with 30 treatment-naive patients
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“Several other findings support central AVP overexpression in these animals [66], which is caused by a genetic variation in the promoter region of the AVP gene [67].”
Background
Synthesis and evaluation of potent and selective human V1a receptor antagonists as potential ligands for PET or SPECT imaging
Fabio, K. M., Guillon, C., Lacey, C. J., Lu, S., Heindel, N. D., Ferris, C. F., Placzek, M. S., Jones, G. B., Brownstein, M., & Simon, N. G. (2011) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2011.12.013 · Cited by 24
Synthesis of [11C]SSR149415 and preliminary imaging studies using positron emission tomography
Schönberger, M., Leggett, C. S., Kim, S. W., & Hooker, J. M. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.03.108 · Cited by 24
From vasotocin to stress and cognition
de Kloet, E. R. (2009) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2009.10.017 · Cited by 22
Lead (Pb) exposure induces physiological alterations in the serotoninergic and vasopressin systems causing anxiogenic-like behavior in Meriones shawi: Assessment of BDMC as a neuroprotective compound for Pb-neurotoxicity and kidney damages
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Restoration of peripheral V2 receptor vasopressin signaling fails to correct behavioral changes in Brattleboro rats
Balázsfi, D., Pintér, O., Klausz, B., Kovács, K., Fodor, A., Török, B., Engelmann, M., & Zelena, D. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.09.011 · Cited by 21
“The literature is rich in articles describing the role of AVP in anxiety and depression (e.g. (Landgraf and Wigger, 2002, Scott and Dinan, 2002, Griebel et al., 2003, Keck, 2006, Landgraf, 2006, Frank and Landgraf, 2008, Simon et al., 2008, Surget and Belzung, 2008, Ryckmans, 2010).”
Background
Vasopressinergic control of stress-related behavior: studies in Brattleboro rats
Csikota, P., Fodor, A., Balázsfi, D., Pintér, O., Mizukami, H., Weger, S., Heilbronn, R., Engelmann, M., & Zelena, D. (2016) · Stress · doi:10.1080/10253890.2016.1183117 · Cited by 21
“However, it is important to be aware of the limited effect of AVP circulating in the blood directly on brain functions (Landgraf, 2006).”
Background
Protective Role and Functional Engineering of Neuropeptides in Depression and Anxiety: An Overview
Okdeh, N., Mahfouz, G., Harb, J., Sabatier, J., Roufayel, R., Gazo-Hanna, E., Kovacic, H., & Fajloun, Z. (2023) · Bioengineering · doi:10.3390/bioengineering10020258 · Cited by 19
Vasopressin Surrogate Marker Copeptin as a Potential Novel Endocrine Biomarker for Antidepressant Treatment Response in Major Depression: A Pilot Study
Agorastos, A., Sommer, A., Heinig, A., Wiedemann, K., & Demiralay, C. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00453 · Cited by 18
“Polymorphisms in the promoter structures of the AVP gene and V1b receptor genes, could thus contribute to individual variation in stress resilience but also phenotypic expression of stress-related disorders and represent a promising target for pharmacotherapeutic interventions (75).”
Background
Combination therapy with neuropeptides for the treatment of anxiety disorder
Gupta, P. R., & Prabhavalkar, K. S. (2021) · Neuropeptides · doi:10.1016/j.npep.2021.102127 · Cited by 17
Naturally occurring variations in defensive burying behavior are associated with differences in vasopressin, oxytocin, and androgen receptors in the male rat
Linfoot, I., Gray, M. E., Bingham, B., Williamson, M., Pinel, J. P. J., & Viau, V. (2009) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2009.06.008 · Cited by 17
“In humans and rodents, CRH and AVP may contribute to extreme trait anxiety and the comorbid expression of depression-like symptoms (Keck, 2006; Landgraf, 2006), whereas OT appears to possess anxiolytic properties (de Wied et al.”
Background
Increased plasma norepinephrine concentration in psychotic depression
Goekoop, J. G., de Winter, R. F. P., Wolterbeek, R., Van Kempen, G. M. J., & Wiegant, V. M. (2012) · Therapeutic Advances in Psychopharmacology · doi:10.1177/2045125312436574 · Cited by 16
“The potential role of increased release of NE next to the increased NE–AVP correlation in PSDEP may be seen in the context of the vasopressinergic mechanisms in animal models of depression [Aguilera et al. 2008; Landgraf, 2006] and noradrenergic mechanisms involved in the hypothalamus–pituitary–adrenal (HPA) axis.”
Background
Effect of arginine vasopressin on the behavioral activity in the behavior despair depression rat model
Yang, J., Pan, Y.-J., Yin, Z., Hai, G.-F., Lu, L., Zhao, Y. Y., Wang, D., Wang, H., & Wang, G. (2012) · Neuropeptides · doi:10.1016/j.npep.2012.03.003 · Cited by 16
“There is also substantial evidence that AVP is an important anxiogenic factor (Landgraf, 2006; Landgraf et al., 2007; Ring, 2005).”
Background
Support for two increased vasopressinergic activities in depression at large and the differential effect of antidepressant treatment
Jg, G., de Winter, R., Wolterbeek, R., & Wiegant, V. M. (2010) · Journal of Psychopharmacology · doi:10.1177/0269881110372549 · Cited by 16
“A more complex variant of stress-induced vasopressinergic co-activation of the HPA axis, which comprises parvocellular and magnocellular AVP synthesis and release, has been found in the genetically inbred high-anxiety behaviour (HAB) rat model (Landgraf, 2006).”
Background
Hippocampus and Hypothalamus RNA-sequencing of WFS1-deficient Mice
Ivask, M., Pajusalu, S., Reimann, E., & Kõks, S. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.039 · Cited by 16
Gene expression profiling in the stress control brain region hypothalamic paraventricular nucleus reveals a novel gene network including Amyloid beta Precursor Protein
Tsolakidou, A. F., Czibere, L., Pütz, B., Trümbach, D., Panhuysen, M., Deussing, J. M., Wurst, W., Sillaber, I., Landgraf, R., Holsboer, F., et al. (2010) · BMC Genomics · doi:10.1186/1471-2164-11-546 · Cited by 17
Self-citation
Hypothalamic stress systems in mood disorders
(2021) · Handbook of Clinical Neurology · doi:10.1016/b978-0-12-819973-2.00003-4 · Cited by 15
Molecular Biological Aspects of Depressive Disorders: A Modern View
Ushakova, V. M., Morozova, A. Y., Reznik, A. M., Kostyuk, G. P., & Chekhonin, V. P. (2020) · Molecular Biology · doi:10.1134/s0026893320050118 · Cited by 16
The Potential Role of Glucocorticoids and the HPA Axis in Alcohol Dependence
Stephens, M. A. C., McCaul, M. E., & Wand, G. S. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-405941-2.00021-3 · Cited by 19
Oxytocin/vasopressin-like neuropeptide signaling in insects
Muratspahić, E., Monjon, E., Duerrauer, L., Rogers, S. M., Cullen, D. A., Broeck, J. V., & Gruber, C. W. (2020) · Vitamins and hormones · doi:10.1016/bs.vh.2019.08.011 · Cited by 15
“…Douglas, & Neumann, 2005; Wersinger, Ginns, O’Carroll, Lolait, & Young, 2002), attachment (Insel & Young, 2001), anxiety-related behavior (Landgraf, 2006), fear conditioning (Eckstein et al., 2015), labor (Gruber & O’Brien, 2011), social recognition (Kirsch et al., 2005), and memory and…”
From the Stalk to Down Under about Brain Glucocorticoid Receptors, Stress and Development
de Kloet, E. R., Han, F., & Meijer, O. C. (2007) · Neurochemical Research · doi:10.1007/s11064-007-9520-9 · Cited by 14
“Such imbalance may be due to inadequate or excessive corticosteroid action or related variants in MR and GR, that are of genetic origin or induced by environmental factors going back as far as perinatal experiences [15, 33, 34].”
Background
Receptor–Ligand Interaction Measured by Inductively Coupled Plasma Mass Spectrometry and Selenium Labeling
Cheignon, C., Cordeau, E., Prache, N., Cantel, S., Martínez, J., Subra, G., Arnaudguilhem, C., Bouyssière, B., & Enjalbal, C. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b01320 · Cited by 14
Differential sensitisation to central cardiovascular effects of angiotensin II in rats with a myocardial infarct: Relevance to stress and interaction with vasopressin
Cudnoch‐Jędrzejewska, A., Szczepanska‐Sadowska, E. K., Dobruch, J. T., Puchalska, L., Ufnal, M., Kowalewski, S., & Wsół, A. (2008) · Stress · doi:10.1080/10253890701794445 · Cited by 11
“…such vital functions as thirst and sodium appetite, and in the release of the hypothalamic and pituitary hormones (Armando et al. 2002; Carrasco and Van de Kar 2003; Fitzsimons 1979; Kovacs and Sawchenko 1996; Landgraf 2006; Mayorov et al. 2004; Saad and Camargo 2003; Saavedra et al. 2005, 2006).”
Background
Contrasting central and systemic effects of arginine-vasopressin on urinary marking behavior as a social signal in male mice
Higuchi, Y., & Arakawa, H. (2022) · Hormones and Behavior · doi:10.1016/j.yhbeh.2022.105128 · Cited by 9
Chapter 4.1 Peptide receptor ligands to treat anxiety disorders
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Paraventricular Nucleus V1a Receptor Knockdown Blunts Neurocardiovascular Responses to Acute Stress in Male Rats after Chronic Mild Unpredictable Stress
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Evidence of vasopressinergic-noradrenergic mechanisms in depression with above-normal plasma vasopressin concentration with and without psychotic features
Goekoop, J. G., de Winter, R. F. P., Wolterbeek, R., Kempen, G. M. J. V., & Wiegant, V. M. (2009) · Journal of Psychopharmacology · doi:10.1177/0269881109349839 · Cited by 9
“The High Anxiety-related Behaviour (HAB) rat, which has been developed by inbreeding for the trait of avoiding an anxiety-provoking condition, has been found to be characterized by increased synthesis and release of AVP, and by high anxiety combined with high immobility after stress (Landgraf, 2006).”
Background
Animal models of anxiety
Schmidt, M. V., & Müller, M. B. (2006) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2006.11.002 · Cited by 10
The involvement of neuropeptides in evolution, signaling, behavioral regulation and psychopathology: focus on vasopressin
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Self-citation

Authors: Landgraf, R.
Affiliations: Max Planck Institute of Psychiatry (DE)
Corresponding author: Landgraf, Rainer
Venue: CNS & Neurological Disorders - Drug Targets
Publisher: Bentham Science Publishers Ltd.
Published: 2006-04-01
Volume: 5
Issue: 2
Pages: 167-179
ISSN: 1568-007X (ISSN-L)
1871-5273
DOI: 10.2174/187152706776359664
OpenAlex: W2027012370
Cited by: 127
References: 0
Citations by year: 2025: 3 · 2024: 2 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 6 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 2 · 2015: 1 · 2014: 7 · 2013: 6 · 2012: 8
FWCI: 22.44
Type: journal article
Language: en
Open access: closed
Locations: CNS & Neurological Disorders - Drug Targets (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Keywords: vasopressin, vasopressin receptor, V1a receptor, V1b receptor, stress-related disorders, anxiety disorders, comorbid depression, hypothalamic paraventricular nucleus, trait anxiety, gene expression, neuroendocrine regulation, stress response, individual variation in behavior, therapeutic target
MeSH terms: Animals, Anxiety Disorders, Arginine Vasopressin, Gene Expression Regulation, Humans, Hypothalamo-Hypophyseal System, Paraventricular Hypothalamic Nucleus, Stress, Physiological, Receptors, Vasopressin, Mood Disorders, Genetic Predisposition to Disease

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The Involvement of the Vasopressin System in Stress-Related Disorders

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