Vasopressin Stimulates Ventromedial Hypothalamic Neurons via Oxytocin Receptors in Oxytocin Gene Knockout Male and Female Mice
Abstract
A wealth of neuropharmacological data demonstrates that oxytocin (OT) actions in the mammalian forebrain support a wide variety of affiliative behaviors and repress aggressive behaviors. Based on that literature, it was expected that reproductive and affiliative behaviors would be vastly decreased and aggression markedly increased in OT gene knockout (OTKO) mice. The initial publications reporting the behaviors of these mice did not include such phenotypes. Here, we compared single-unit activities recorded from the ventromedial hypothalamus in tissue slices of male and female OTKO mice and their wild-type littermate to test two hypotheses about OT functional genomics. First, we proposed that in OTKO mice, a very similar 9-amino-acid neuropeptide, arginine vasopressin (a likely gene duplication product), can ‘cross over’ and compensate for the lack of OT. This hypothesis was confirmed in both males and females. Further, we proposed that because of the lifelong absence of OT in OTKO, OT receptors would be more sensitive to OT in the knockout animals. We tested this idea in males and found that it was correct. Thus, an answer to the ‘OTKO paradox’ is put forth, with implications for OT-sensitive behaviors in a variety of species.
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Several previous studies suggested that the effects of oxytocin and vasopressin result from activation of the opposite receptor.
“This concept is not new; several previous studies suggested that the effects of OT and AVP are a result of the activation of the ‘opposite’ receptor (4,80,86-89).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [86]
There can be substantial cross-talk between OT and AVP and OTRs and V1aRs.
“Because OT and AVP as well as their canonical receptors display strikingly similar chemical structures, it is not surprising that there can be substantial cross-talk between these peptides and OTRs and V1aRs [79].”
From Cross-talk among oxytocin and arginine-vasopressin receptors: Relevance for basic and clinical studies of the brain and periphery (2018) · cites this paper as [79]
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- Authors
- Ragnauth, A. K., Goodwillie, A., Brewer, C., Muglia, L. J., Pfaff, D. W., & Kow, L.-M.
- Affiliations
- Rockefeller University (US)
- New York University (US)
- Washington University in St. Louis (US)
- Venue
- Neuroendocrinology
- Publisher
- S. Karger AG
- Published
- 2004
- Volume
- 80
- Issue
- 2
- Pages
- 92-99
- ISSN
- 0028-3835 (ISSN-L)
- 1423-0194
- OpenAlex
- W2016001259
- Cited by
- 41
- References
- 59
- Citations by year
- 2024: 3 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 2
- FWCI
- 3.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 38273, R01MH038273)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin, vasopressin, oxytocin receptor, ventromedial hypothalamus, single-unit activity, gene duplication, affiliative behavior, aggression, sex differences, functional genomics
- MeSH terms
- Animals, Arginine Vasopressin, Evoked Potentials, Female, Hypothalamus, Male, Neurons, Organ Culture Techniques, Oxytocin, Sex Factors, Vasopressins, Receptors, Vasopressin, Receptors, Oxytocin, Mice, Knockout, Patch-Clamp Techniques, Mice, Antidiuretic Hormone Receptor Antagonists
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