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Reduced Aggressive Behaviour in Mice with Targeted Disruption of the Oxytocin Gene
Abstract
Oxytocin (OT) has been reported to mediate aggressive and affiliative behaviours in several species. The behavioural role of OT has been established with physiological manipulations that potentially affected blood pressure, which may have indirectly affected the behaviours under study. To provide converging evidence of the physiological role of OT in aggressive behavior, wild type (WT), heterozygous (OT-/+), and homozygous (OT-/-) mutant mice were tested in two aggression paradigms. In general, there was no significant difference in aggressiveness between WT and OT-/+ mice. However, there were significant reductions in the duration of aggressive behaviors among OT-/- animals, especially in agonistic encounters within neutral arenas. The OT-/- mice did not exhibit any sensorimotor deficits or display any altered general anxiety levels that may have accounted for the observed reduction in aggressive behavior. These data indicate that aggression is mediated in part by OT in mice and that increased aggressiveness is not an obligatory phenotypic result of targeted genetic disruption of any gene.
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“In mice, there is evidence that in utero exposure to Oxt is important for normal intermale aggressive behavior in adulthood.”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [98]
In the citing paper
“Specifically, male Oxt−/− mice that are born to null mutant dams show heightened aggressive behavior in adulthood (97, 98).”
From Oxytocin during Development: Possible Organizational Effects on Behavior (2015) · cites this paper as [98]
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Pobbe, R. L. H., Pearson, B. L., Defensor, E. B., Bolivar, V. J., Young, W. S., Lee, H., Blanchard, D. C., & Blanchard, R. J. (2011) · Hormones and Behavior · doi:10.1016/j.yhbeh.2011.10.010 · Cited by 143
“Importantly, studies examining the behavioral performance of mice with targeted mutation in the Oxt gene have consistently revealed deficits in social memory, reduced aggression, and normal social approach for this group, as compared to WT (Crawley et al., 2007; DeVries et al., 1997; Ferguson et al., 2001; Winslow and…”
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Takahashi, A., Quadros, I. M., de Almeida, R. M. M., & Miczek, K. A. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2000-y · Cited by 140
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Takahashi, A., Quadros, I. M., de Almeida, R. M. M., & Miczek, K. A. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_191 · Cited by 123
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Behavior in Mice with Targeted Disruption of Single Genes
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A Role for Oxytocin in the Etiology and Treatment of Schizophrenia
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“Oxt−/− and Oxtr−/− mice have increases in aggressive behavior, and given the dysregulation of the Oxt system in schizophrenia, a functional Oxt system could be important for normal aggressive behavior (32, 90, 131, 153, 157, 158).”
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“…two different research groups, the reports on male aggressive behavior, as measured using a resident–intruder behavioral test, were conflicting, with one group reporting reduced aggressive behavior (DeVries et al., 1997) and the other reporting heightened aggressive behavior (Winslow et al., 2000).”
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Targeted Reduction of Oxytocin Expression Provides Insights into its Physiological Roles
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Self-citationThe Prolactin Family of Hormones as Regulators of Maternal Mood and Behavior
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“Importantly, the lack of maternal OT during fetal life of male mice might cause a heightened aggressive behavior in adulthood (Winslow et al. 2000; DeVries et al. 1997).”
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“While OXT, AVP, and their receptors have been studied extensively in rodent aggression using pharmacologic reagents and zygotic gene knockouts, 32,56,80–83 there are no reports of a spe-cific requirement in offensive aggression for either Oxtr or Avpr1a in murine VMHvl.”
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“Concerning the fascinating finding that interspersed and even identical neurons are involved in both aggression andmating, the following, more circumstantial, points can be considered in addition: – Lesions in or knife cuts along the lateral side of the VMH affect not only mating (Mathews and Edwards, 1977a; Pfaff and…”
InfluentialAntisocial Personality Disorder
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Oxytocin modulates social interaction but is not essential for sexual behavior in male mice
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“Ž .2000 , but not all Devries et al., 1997 , studies.”
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“, 2020); conditional knock-out of OXTRs in this region impairs social recognition (DeVries et al., 1997; Ferguson et al., 2001; Wang et al., 2018).”
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“However, all these ligands also bind vasopressin receptors.”
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“The pituitary peptide AVP acts to augment HPA response peripherally and plays a role in augmenting social aggression centrally [Compaan et al., 1993; DeVries et al., 1997; DeVries&Miller, 1998; Ferris & Delville, 1994; Nelson & Chiavegatto, 2001].”
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“The expression of AVP is greater in male than female brains in various species [63], and AVP is typically associated with male-typical social behaviors, such as male reproduction, aggression and territoriality [90].”
BackgroundUchida, S., Fuke, S., & Tsukahara, T. (2006) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21094 · Cited by 22
“This phenomenon of OTR along with the generation of OT gene knockout mice (OTKO mice) [Nishimori et al., 1996; Young et al., 1996; DeVries et al., 1997; Wagner et al., 1997] suggest that the upregulation of OTR is necessary for the cardiomyocyte differentiation processes.”
BackgroundZhang, Y., Wu, C., Chang, H., Yan, Q., Wu, L., Yuan, S., Xiang, J., Hao, W., & Yu, Y. (2017) · Journal of Affective Disorders · doi:10.1016/j.jad.2017.12.024 · Cited by 23
Aggressive behavior in transgenic animal models: A systematic review
Jager, A., Maas, D. A., Fricke, K., de Vries, R. B., Poelmans, G., & Glennon, J. C. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2017.09.028 · Cited by 21
“Oxt OT, HET no change Increased attack latency, decreased number of attacks (DeVries et al., 1997)”
Evaluation of hypothalamic gene expression in mice divergently selected for heat loss
Wesolowski, S. R., Allan, M. F., Nielsen, M. K., & Pomp, D. (2003) · Physiological Genomics · doi:10.1152/physiolgenomics.00184.2002 · Cited by 20
“Oxt mutant null mice show reduced aggressive behavior (6, 42).”
BackgroundLoParo, D., Johansson, A., Walum, H., Westberg, L., Santtila, P. O., & Waldman, I. D. (2015) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32359 · Cited by 21
“Our findings are consistent with studies suggesting thatOXT is associatedwith aggression in a variety of animal [DeVries et al., 1997; Harmon et al., 2002; Winslowand Insel, 2002; Lubin et al., 2003;Ragnauth et al., 2005] and human [Fetissov et al., 2006; Lee et al., 2009; Jokinen et al., 2012]…”
ResultUsing transgenic mouse models to study oxytocin's role in the facilitation of species propagation
Lee, H., Pagani, J. H., & Young, W. S. (2010) · Brain Research · doi:10.1016/j.brainres.2010.08.042 · Cited by 21
“Initially, one line with inactivation of the oxytocin gene was shown to be mildly less aggressive than WT or HET controls, and showed no difference in anxiety behavior in an open field (DeVries et al., 1997).”
Self-citationOxytocin Signaling Acts as a Marker for Environmental Stressors in Zebrafish
Chuang, H.-J., Chang, C.-Y., Ho, H.-P., & Chou, M. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147459 · Cited by 20
“Through aggressive behavior, animals consolidate resources and status in society [83].”
BackgroundOxytocin and CD38 in the paraventricular nucleus play a critical role in paternal aggression in mice
Shabalova, A. A., Liang, M., Zhong, J., Huang, Z., Tsuji, C., Shnayder, N. A., Lopatina, O. L., Salmina, A. B., Okamoto, H., Yamamoto, Y., et al. (2020) · Hormones and Behavior · doi:10.1016/j.yhbeh.2020.104695 · Cited by 18
Maternal aggression driven by the transient mobilisation of a dormant hormone-sensitive circuit
Stagkourakis, S., Williams, P., Spigolon, G., Khanal, S., Ziegler, K., Heikkinen, L., Fisone, G., & Broberger, C. (2025) · Nature Communications · doi:10.1038/s41467-025-64043-4 · Cited by 17
Alone, in the dark: The extraordinary neuroethology of the solitary blind mole rat
Kashash, Y., Smarsh, G. C., Zilkha, N., Yovel, Y., & Kimchi, T. (2022) · eLife · doi:10.7554/elife.78295 · Cited by 16
Guoynes, C. D., & Marler, C. A. (2021) · Physiology & Behavior · doi:10.1016/j.physbeh.2022.113773 · Cited by 13
Behavioral Roles of Oxytocin and Vasopressin
Benjamin, C. (2012) · InTech eBooks · doi:10.5772/50422 · Cited by 14
“Disruption of the OXT gene in male mice decreases aggression [12], yet OXT”
BackgroundClarke, L., Zyga, O., Pineo-Cavanaugh, P. L., Jeng, M., Fischbein, N. J., Partap, S., Katznelson, L. J., & Parker, K. J. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104770 · Cited by 13
Neuroendocrinology of Aggression
Trainor, B. C., & Nelson, R. J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-375097-6.10022-8 · Cited by 12
Self-citationWatve, M. (2012) · Springer eBooks · doi:10.1007/978-1-4614-4409-1_7 · Cited by 13
Moore, J. L., Kennedy, J. P., & Hassan, A.-A. (2024) · Frontiers in Neuroscience · doi:10.3389/fnins.2024.1489308 · Cited by 11
Powers, K. G., Ma, X., Eipper, B. A., & Mains, R. E. (2020) · Genes Brain & Behavior · doi:10.1111/gbb.12699 · Cited by 13
“contrast, male oxytocin gene-knockout mice show a reduction in the duration of aggressive behavior when compared tomale controls.(76) Sexdependent behavioral differences in Pam mice may well be attributable to differences in oxytocin.”
BackgroundTransgenic Models for Studies of Oxytocin and Vasopressin
Gainer, H., & Young, W. S. (2001) · Endocrine updates · doi:10.1007/978-1-4615-1633-0_2 · Cited by 11
“Furthermore, a number of behaviors, including sexual and maternal, are minimally, if at all, affected (72, 79 ).”
BackgroundSelf-citationA disparity between locomotor economy and territory holding ability in male house mice
Morris, J. S., Ruff, J. S., Potts, W. K., & Carrier, D. R. (2017) · Journal of Experimental Biology · doi:10.1242/jeb.154823 · Cited by 8
“House mice have a polygynous mating system in which territory control among males is determined by frequent and intense fighting, resulting in a high incidence of injury and even death (Brown, 1953; DeVries et al., 1997; Demas et al., 1999).”
BackgroundChapter 4.1 Peptide receptor ligands to treat anxiety disorders
Steckler, T. (2008) · Handbook of behavioral neuroscience · doi:10.1016/s1569-7339(07)00010-0 · Cited by 10
Metadata
- Authors
- DeVries, A. C., Young III, W. S., & Nelson, R. J.
- Affiliations
- National Institutes of Health (US)
- Johns Hopkins University (US)
- Corresponding author
- DeVries, A. Courtney
- Venue
- Journal of Neuroendocrinology
- Publisher
- Wiley
- Published
- 1997-05
- Volume
- 9
- Issue
- 5
- Pages
- 363-368
- ISSN
- 0953-8194 (ISSN-L)
- 1365-2826
- OpenAlex
- W1989283759
- Cited by
- 134
- References
- 0
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 2 · 2018: 5 · 2017: 7 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Syracuse University
- National Institutes of Health (5r01hd022201-06)
- National Institute of Mental Health (MH-57535, R01MH057535)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 22201)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › 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, aggression, gene disruption, affiliative behavior, agonistic encounters, anxiety, sensorimotor deficits, blood pressure
- MeSH terms
- Aggression, Animals, Exploratory Behavior, Genetic Code, Heterozygote, Homozygote, Oxytocin, Psychomotor Performance, Mice, Knockout, Mice
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