Heightened aggressive behavior in mice with lifelong versus postweaning knockout of the oxytocin receptor
Abstract
Previous work implicating the neuropeptide oxytocin (Oxt) in the neural regulation of aggression in males has been limited. However, there are reports of heightened aggression in Oxt knockout and Oxt receptor (Oxtr) knockout male mice when they are born to null mutant mothers; suggesting that intrauterine exposure to Oxt may be important to normal aggression in adulthood. To explore this, we examined aggression in two lines of Oxtr mice, a total knockout (Oxtr-/-), in which the Oxtr gene is absent from the time of conception, and a predominantly forebrain specific knockout (Oxtr FB/FB), in which the Oxtr gene is not excised until approximately 21-28days postnatally. Aggression was measured in males from both lines, as well as control littermates, using a resident-intruder behavioral test. Consistent with previous reports, male Oxtr-/- mice had elevated levels of aggression relative to controls. Oxtr FB/FB mice on the other hand displayed levels of aggression similar to control animals. In addition, following a resident-intruder test, Oxtr+/+ mice that displayed aggression had less c-fos immunoreactivity in the ventral portion of the lateral septum than those that did not. Further, Oxtr-/- mice had increased c-fos immunoreactivity in the medial amygdala relative to controls. These data suggest that Oxt may play an important role during development in the organization of the neural circuits that underlie aggressive behavior in adulthood, with its absence resulting in heightened aggression.
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Several studies have demonstrated a reduction in aggressive behaviors upon treatment with exogenous OT or an increase in such behaviors in animals genetically lacking OT or OTR.
“Several studies have employed the RI paradigm to demonstrate a reduction in aggressive behaviors upon treatment with exogenous OT (Calcagnoli et al., 2013, Calcagnoli et al., 2014, Calcagnoli et al., 2015, Jong et al., 2014, Karpova et al., 2016) or an increase in such behaviors in animals genetically lacking OT or OTR (Dhakar et al., 2012, Pagani et al., 2015, Ragnauth et al., 2005, Takayanagi et”
From Wireless Optogenetic Stimulation of Oxytocin Neurons in a Semi-natural Setup Dynamically Elevates Both Pro-social and Agonistic Behaviors (2020) · cites this paper as Dhakar et al., 2012
Male Oxtr knockout mice have heightened aggressive behavior in adulthood.
“These mice also have heightened aggressive behavior in adulthood (99, 100).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [100]
Studies using male Oxtr knockout mice support the hypothesis that maternal Oxt may be signaling in the fetal brain.
“The hypothesis that the maternal Oxt may be signaling in the fetal brain is supported by studies using male Oxtr knockout (Oxtr−/−) mice, which lack Oxtr signaling throughout development.”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [100]
Male forebrain Oxtr knockout mice, in which the Oxtr gene is excised 21-28 days after birth, have normal aggressive behavior in adulthood.
“However, male forebrain Oxtr knockout (Oxtr Fb/Fb) mice (101, 102), in which the Oxtr gene is excised 21–28 days after birth, have normal aggressive behavior in adulthood (100).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [100]
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- Authors
- Dhakar, M. B., Rich, M. E., Reno, E. L., Lee, H.-J., & Caldwell, H. K.
- Affiliations
- Kent State University (US)
- Kyungpook National University (KR)
- Corresponding author
- Caldwell, Heather K.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2012-06
- Volume
- 62
- Issue
- 1
- Pages
- 86-92
- ISSN
- 0018-506X (ISSN-L)
- OpenAlex
- W1978235107
- Cited by
- 54
- References
- 55
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 6 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 3 · 2016: 7 · 2015: 6 · 2014: 7 · 2013: 4
- FWCI
- 8.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Kent State University
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- oxytocin, oxytocin receptor, aggression, knockout mice, resident-intruder test, c-fos, lateral septum, medial amygdala, neural circuit development, male aggression, prenatal exposure
- MeSH terms
- Aggression, Amygdala, Animals, Male, Oxytocin, Septal Nuclei, Proto-Oncogene Proteins c-fos, Receptors, Oxytocin, Mice, Knockout, Mice
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