Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior

Hodgson, Robert A.; Mullins, Deborra; Lu, Sherry X.; Guzzi, Mario; Zhang, Xiaoping; Bleickardt, Carina J.; Scott, Jack D.; Miller, Michael W.; Stamford, Andrew W.; Parker, Eric M.; Varty, Geoffrey B.

doi:10.1016/j.ejphar.2014.02.027

Cited by 30Stress Responses and CortisolNeuroendocrine regulation and behaviorNeuropeptides and Animal Physiology

Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior

Hodgson, Robert A., Mullins, Deborra, Lu, Sherry X., Guzzi, Mario, Zhang, Xiaoping, Bleickardt, Carina J., Scott, Jack D., Miller, Michael W. +3 more·2014·European Journal of Pharmacology

DOI 10.1016/j.ejphar.2014.02.027

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Abstract

Overactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to affective disorders such as anxiety and depression. Dampening HPA activity has, therefore, been considered as a possible means of treating affective disorders. Given the important role of vasopressin in modulating the HPA axis, one strategy has focused on inhibiting activity of the vasopressin 1b (V1b) receptor. In animals, V1b receptor antagonists reduce plasma stress hormone levels and have been shown to have an anxiolytic-like effect. Recently, V1B-30N was identified as a highly potent V1b receptor antagonist with selectivity over other vasopressin receptors, which is evaluated here in rodent models of anxiety-like and depression-like behaviors. V1B-30N (1-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in rat pups without producing any sedative effects in the animals. Similarly, V1B-30N (3-30mg/kg, IP) dose-dependently reduced separation-induced vocalizations in guinea pig pups. In a conflict assay, conditioned lick suppression, V1B-30N (3-30mg/kg, IP) increased punished licking. To assess antidepressive-like properties, V1B-30N (1-30mg/kg) was tested in the mouse and rat forced-swim tests but was found to be inactive. These results are consistent with previous findings with other V1b antagonists, which suggest that acute pharmacological antagonism of the V1b receptor has anxiolytic-like but not antidepressant-like properties.

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V1A and V1B receptor antagonists have demonstrated anxiolytic and antidepressant effects in preclinical studies.
“Indeed, V 1A and V 1B receptor antagonists have demonstrated anxiolytic and antidepressant effects in preclinical studies (Bleickardt et al., 2009;Hodgson et al., 2014).”
From Novel pharmacological targets in drug development for the treatment of anxiety and anxiety-related disorders (2019) · cites this paper as Hodgson et al., 2014

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Authors: Hodgson, R. A., Mullins, D., Lu, S. X., Guzzi, M., Zhang, X., Bleickardt, C. J., Scott, J. D., Miller, M. W., Stamford, A. W., Parker, E. M., & Varty, G. B.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Corresponding author: Hodgson, Robert A.
ORCID: Zhang, Xiaoping
Scott, Jack D.
Stamford, Andrew W.
Varty, Geoffrey B.
Venue: European Journal of Pharmacology
Publisher: Elsevier BV
Published: 2014-05
Volume: 730
Pages: 157-163
ISSN: 0014-2999 (ISSN-L)
DOI: 10.1016/j.ejphar.2014.02.027
OpenAlex: W2036871700
Cited by: 30
References: 33
Citations by year: 2024: 8 · 2023: 2 · 2022: 1 · 2021: 4 · 2019: 3 · 2018: 4 · 2017: 2 · 2016: 3 · 2015: 2 · 2014: 1
FWCI: 1.31
Type: journal article
Language: en
Open access: closed
Locations: European Journal of Pharmacology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: vasopressin, anxiety-like behavior, depression-like behavior, hypothalamic-pituitary-adrenal axis, anxiolytic effects, antidepressant effects, forced swim test, stress hormones
MeSH terms: Animals, Antidepressive Agents, Anxiety, Behavior, Animal, Conditioning, Psychological, Depression, Female, Guinea Pigs, Male, Swimming, Anti-Anxiety Agents, Vocalization, Animal, Receptors, Vasopressin, Mice, Rats, Antidiuretic Hormone Receptor Antagonists

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Characterization of a novel vasopressin V1b receptor antagonist, V1B-30N, in animal models of anxiety-like and depression-like behavior

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