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The Involvement of the Vasopressin System in Stress-Related Disorders
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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“Its central actions are mediated by binding to the two G-protein coupled V 1A and V 1B receptors which are distributed in many anxiety-and fear-related brain areas including in the lateral septum, cortex and hippocampus, with V 1A receptors being the predominant receptor (Landgraf, 2006).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Landgraf, 2006
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Items 101–127 of 127
Arakawa, H., & Higuchi, Y. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104597 · Cited by 8
Holsboer, F., & Ising, M. (2024) · Pharmacopsychiatry · doi:10.1055/a-2372-3549 · Cited by 8
“It is important to understand the following strategy in the development of a companion test allowing to predict which patient with depression will benefit from treatment with vasopressin type1(V1b-) receptor antagonists [77].”
InfluentialМолекулярно-биологические аспекты депрессивных состояний: современный взгляд на проблему
Ushakova, V. M., Морозова, А. Ю., Reznik, A. M., Kostyuk, G. P., & Chekhonin, V. P. (2020) · Molecular Biology · doi:10.31857/s0026898420050110 · Cited by 8
Amygdala AVPR1A mediates susceptibility to chronic social isolation in femalesPreprint
François, M., Delgado, I. C., Lafond, A., Lewis, E. M., Kuromaru, M., Hassouna, R., Deng, S., Thaker, V., Dölen, G., & Zeltser, L. M. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.02.15.528679 · Cited by 7
“, 2005), and it is known to contribute to the pathophysiology of emotional and social 60 disorders that have sex-biases (Heinrichs and Domes, 2008; Landgraf, 2006; Meyer-Lindenberg 61 et al., 2011; Neumann and Landgraf, 2012), but its role in the amygdala is less studied.”
BackgroundCorticotropin-Releasing Hormone Peptide Family
Hogg, D. W., Husić, M., & Lovejoy, D. A. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.95738-6 · Cited by 4
Amygdala AVPR1A mediates susceptibility to chronic social isolation in female mice
François, M., Vranich, K. A., Delgado, I. C., Lafond, A., Lopatinsky, N. R., Davis, T., Lewis, E. M., Kuromaru, M., Hassouna, R., Williams, B. L., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-64742-y · Cited by 11
“Anxiogenic AVPR1A CeA circuits are distinct Amygdala activation is associated with anxiety in humans 34 and exogenous stimulation of several subpopulations of CeA neurons is suf-fi cient to induce anxiety-related behaviors in rodents.”
Podtschaske, A. H., Martin, J., Ulm, B., Jungwirth, B., & Kagerbauer, S. M. (2022) · BMC Neuroscience · doi:10.1186/s12868-022-00757-1 · Cited by 2
“Moreover, it can be released via a somato-dendritic pathway within the brain where it modulates behavioral patterns like aggression or pair bonding and contributes to stress-related behavior and anxiety [2].”
BackgroundIsing, M., Holsboer, F., Myhsok, M., & Müller‐Myhsok, B. (2025) · Pharmacopsychiatry · doi:10.1055/a-2508-5834 · Cited by 2
“These findings also alingn with the observation of increased AVP expression in rodents selectively bred for anxiety-like behaviour [15].”
Genetic Transmission of Behavior and Its Neuroendocrine Correlates
Hambsch, B., Landgraf, R., Czibere, L., & Touma, C. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00084-x · Cited by 3
Self-citationHypothalamic–Pituitary–Adrenal Cortical Axis
Rhodes, M. E., McKlveen, J. M., Ripepi, D. R., & Gentile, N. E. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00073-5 · Cited by 5
Monitoring oxytocin signaling in the brain: More than a love story
Neumann, I. D. (2023) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2023.100206 · Cited by 3
“Thus, many details of the complex brain OXT and AVP systems have been revealed until today, but their detailed description goes beyond the scope of this small review, the more as they have been extensively reviewed [5,13 – 15].”
BackgroundBunck, M. (2008) · doi:10.5282/edoc.9109 · Cited by 2
Zukunftsstrategien für die Entdeckung neuer Antidepressiva
Holsboer, F. (2008) · Springer eBooks · doi:10.1007/978-3-540-68748-1_9 · Cited by 2
Differential sensitivity of the Brattleboro rat to glutamatergic and dopaminergic perturbation
Lin, R. E., Suh, J., Ambler, L., Billingslea, E. N., Cho, M., Ciacci, A., Tatard-Leitman, V. M., Featherstone, R. E., & Siegel, S. J. (2014) · Journal of Psychiatry and Brain Functions · doi:10.7243/2055-3447-1-3
“Limitations VP has many important functions including neuromodulation of the HPA axis and the stress response [65].”
BackgroundHerbet, M., Widelski, J., Ostrowska-Leśko, M., Serefko, A., Wojtanowski, K. K., Kurek, J., & Piątkowska‐Chmiel, I. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072884 · Cited by 1
“The nr3c1 gene encodes the glucocorticoid receptor, which binds cortisol, the stress hormone produced by the adrenal glands [58].”
Kellner, M. B. (2008) · Springer eBooks · doi:10.1007/978-3-540-68748-1_15 · Cited by 1
Corticotropin-releasing hormone peptide family
Lovejoy, D. A. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13825-6.00136-9 · Cited by 1
Effects of central neuropeptides on social preference and social recognition in male rats
Lukas, M. (2011) · University of Regensburg Publication Server (University of Regensburg) · doi:10.5283/epub.22540
The role of corticotropin-releasing hormone in REM sleep regulation
Curzi, M. L. (2014) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.16572
Romanowski, C. P. N. (2010) · Elektronische Hochschulschriften der LMU München (Ludwig-Maximilians-Universität München) · doi:10.5282/edoc.11851
Yoshioka, M., Yamaguchi, T., Gyotoku, J.-I., Ochiai, T., & Ohta, H. (2010) · Biological Sciences in Space · doi:10.2187/bss.24.95
“A potential role for AVP in the development and course of depression has been derived from clinical studies that, found elevated AVP concentrations in cerebrospinal fluid (CSF) (de Bellis et al., 1993; Heuser et al., 1998), plasma (van Londen et al., 1997), and PVN neurons (Purba et al., 1996).”
ResultOptimization and characterization of an antagonist for vasopressin 1a (V1a) receptor
Mittapalli, G. K., Argaryan, L., Brown, S. J., Saldanha, S. A., Volmar, C., Ferguson, J., Roberts, E., Hodder, P., & Rosen, H. (2014) · Europe PMC (PubMed Central)
Treating Posttraumatic Stress Disorder: A Timely Update on Therapeutic Strategies
Tucker, L. D., Li, Y., & Zhang, Q. (2020) · Journal of Psychology and Psychotherapy Research · doi:10.12974/2313-1047.2020.07.10
Copeptin response to acute physical stress during hypohydration: An exploratory secondary analysisPreprint
Carroll, H. A., & Melander, O. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.09.19.460958
“Since AVP is a regulator of psychological stress (e.g. depression; Landgrad, 2006), there may be a psychological stress-hydration status interaction for copeptin which does not translate to other stress hormones (in this case ACTH and cortisol, which both responded to stress but not differentially…”
BackgroundKeck, M. E., & Landgraf, R. (2011) · Springer eBooks · doi:10.1007/978-3-642-19844-1_19
Self-citationSteiger, A., Dimopoulou, C., & Stalla, G. K. (2010) · Elsevier eBooks · doi:10.1016/b978-3-437-24680-7.10073-x
Metadata
- 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
- 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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