Social amnesia in mice lacking the oxytocin gene
Abstract
The development of social familiarity in rodents depends predominantly on olfactory cues and can critically influence reproductive success. Researchers have operationally defined this memory by a reliable decrease in olfactory investigation in repeated or prolonged encounters with a conspecific. Brain oxytocin (OT) and vasopressin (AVP) seem to modulate a range of social behaviour from parental care to mate guarding. Pharmacological studies indicate that AVP administration may enhance social memory, whereas OT administration may either inhibit or facilitate social memory depending on dose, route or paradigm. We found that male mice mutant for the oxytocin gene (Oxt-/-) failed to develop social memory, whereas wild-type (Oxt+/+) mice showed intact social memory. Measurement of both olfactory foraging and olfactory habituation tasks indicated that olfactory detection of non-social stimuli is intact in Oxt-/- mice. Spatial memory and behavioural inhibition measured in a Morris water-maze, Y-maze, or habituation of an acoustic startle also seemed intact. Treatment with OT but not AVP rescued social memory in Oxt-/- mice, and treatment with an OT antagonist produced a social amnesia-like effect in Oxt+/+ mice. Our data indicate that OT is necessary for the normal development of social memory in mice and support the hypothesis that social memory has a neural basis distinct from other forms of memory.
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Increasing accumbal oxytocin receptor in female meadow voles was not sufficient to induce partner preference formation in this asocial species.
“However, increasing accumbal OTR in female meadow voles was not sufficient to induce partner preference formation in this asocial species [45].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [45]
Enhancing oxytocin receptor density in the nucleus accumbens of adult female prairie voles using a viral vector did not increase the proportion of females displaying alloparental care towards pups.
“However, there was no difference between OTR viral injected and control groups in the proportion of females displaying alloparental behavior [45].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [45]
OTR-enhanced female prairie voles took less time to form a partner preference than controls, indicating that higher levels of oxytocin receptor in the nucleus accumbens accelerates pair bond formation.
“These OTR-enhanced females took less time to form a partner preference than controls, indicating that higher levels of OTR in the NAcc accelerates pair bond formation (Figure 4C).”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [45]
Previous work in social recognition has shown that mice show both habituation of olfactory responses directed toward an unfamiliar conspecific, and dishabituation, with a reinstatement of social sniffing, when a novel stimulus animal is presented.
“Previous work in social recognition has shown that mice show both habituation of olfactory responses directed toward an unfamiliar conspecific, and dishabituation, with a reinstatement of social sniffing, when a novel stimulus animal is presented (Bluthe et al. 1993;Dluzen & Kreutzberg 1993;Ferguson et al. 2000;Kogan et al. 2000;Winslow & Camacho 1995).”
From Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice (2004) · cites this paper as Ferguson et al. 2000
Social discrimination is a complex behavior, and several other signaling molecules have been shown to play a role in social discrimination, including oxytocin and arginine vasopressin.
“social discrimination is a complex behavior, and several other signaling molecules have been shown to play a role in social discrimination, including oxytocin [35–37] and arginine vasopressin [24, 38–40].”
From Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats (2021) · cites this paper as [37]
The oxytocin and vasopressin systems are involved in recognising individuals as familiar.
“The OT and AVP systems are also involved in more subtle aspects of social cognition, including recognising individuals as familiar (8,9).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [8]
In mouse studies showing the requirement of oxytocin in the medial amygdala for social memory, social memory was measured by habituation of olfactory exploration after repeated presentations.
“For example, in the studies in mice that demonstrated the requirement of OT in the MeA for social memory of a familiar conspecific, social memory was measured by the habituation of time spent in olfactory exploration of the stimulus animal after repeated presentations (8,24).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [8]
Social recognition in OT knock-out male mice is severely impaired.
“For example, social recognition in OT knock-out male mice is severely impaired [68; 69].”
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 [68]
OT KO mice show no deficits in spatial memory, non-social olfactory memory, and habituation, and can retain social memory if intruders are painted with a non-social odor.
“Importantly, the OT KO mice display no deficits in spatial memory, non-social olfactory memory, and habituation, and can retain a social memory if the novel intruders are painted with a non-social odor (Ferguson et al 2000; author’s unpublished data).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Ferguson et al 2000
Mice lacking the OT gene have impaired social memory that can be recovered by OT treatment before the initial social encounter, showing OT at the time of the salient event is necessary and sufficient for social memory.
“Mice lacking the OT gene have impaired social memory that can be recovered by OT treatment prior to the initial social encounter, demonstrating that the presence of OT at the time of the salient event is necessary and sufficient for social memory (Ferguson et al 2000; Ferguson et al 2001).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Ferguson et al 2000
Oxytocin activates social memory areas in the brain.
“It also activates social memory areas in the brain (Dantzer et al., 1987; Ferguson et al., 2000).”
From Endogenous peripheral oxytocin measures can give insight into the dynamics of social relationships: a review (2014) · cites this paper as Ferguson et al., 2000
Centrally administered oxytocin facilitates contact-seeking, attachment bond formation, and social memory in rodents.
“Centrally administered OT facilitates contact-seeking, attachment bond formation, and social memory in rodents (Ferguson et al., 2000; Williams et al., 1992; Witt et al., 1992).”
From Effects of intranasal oxytocin on social anxiety in males with fragile X syndrome (2012) · cites this paper as Ferguson et al., 2000
Social olfactory deficits in mice without the oxytocin gene are rescued with injection of oxytocin into rat olfactory bulbs.
“social olfactory deficits in mice without the oxytocin gene66 are rescued with injection of oxytocin into rat olfactory bulbs67.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [66]
OTKO mice fail to recognize familiar conspecifics.
“Early studies showed that OTKO mice fail to recognize familiar conspecifics (Ferguson et al. 2000) and do not reduce their olfactory investigation even following several encounters.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2000
A central infusion of oxytocin before and not after the first encounter rescues OTKO mice's capacity to recognize a familiar conspecific.
“A central infusion of oxytocin before and not after the first encounter rescues their capacities to recognize a familiar conspecific.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2000
OTKO mice are able to recognize nonsocial olfactory scents, making their deficit selectively a social recognition deficit.
“However, these OTKO mice are able to recognize nonsocial olfactory scents, which make their deficit selectively a social recognition deficit.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2000
OTKO mice do not reduce their olfactory investigation even following several encounters.
“Early studies showed that OTKO mice fail to recognize familiar conspecifics (Ferguson et al. 2000) and do not reduce their olfactory investigation even following several encounters.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2000
Oxytocin knockout mice exhibit social recognition impairments, however, these impairments can be reversed by oxytocin infusion into medial amygdala, indicating special involvement of the amygdala in this process.
“Oxytocin knockout mice also exhibit social recognition impairments, however, these impairments can be reversed by oxytocin infusion into medial amygdala, indicating special involvement of the amygdala in this process (Choleris et al., 2003, Ferguson et al., 2001, Ferguson et al., 2000).”
From Oxytocin, motivation and the role of dopamine (2014) · cites this paper as Ferguson et al., 2000
Four randomized placebo-controlled trials of children and adolescents have employed oxytocin dosages stratified by weight or age.
“Guided by other pharmaceutical trials, four randomized placebo-controlled trials of children and adolescents have employed dosages stratified by weight or age.38,49,51,54”
From Beyond the hype and hope: critical considerations for intranasal oxytocin research in autism spectrum disorder (2017) · cites this paper as [38]
There is some evidence that both rats and mice can recognize individual conspecifics and choose different social behaviors depending on partner's identity.
“There is some evidence that both species can recognize individual conspecifics 52,53 and, depending on partner's identity, choose different social behaviors (see Section 4).”
From Ecological validity of social interaction tests in rats and mice (2019) · cites this paper as [52]
Oxytocin has a well-established role in social behaviors and social recognition.
“and the well-established role of oxytocin in social behaviors and social recognition (13, 21, 34; 39-44).”
From Social Interaction Elicits Activity in Glutamatergic Neurons in the Posterior Intralaminar Complex of the Thalamus (2024) · cites this paper as [21]
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- Authors
- Ferguson, J. N., Young, L. J., Hearn, E. F., Matzuk, M. M., Insel, T. R., & Winslow, J. T.
- Affiliations
- Emory University (US)
- Baylor College of Medicine (US)
- Corresponding author
- Winslow, James T.
- Venue
- Nature Genetics
- Published
- 2000-07
- Volume
- 25
- Issue
- 3
- Pages
- 284-288
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1602757251
- Cited by
- 1,130
- References
- 31
- Citations by year
- 2026: 18 · 2025: 33 · 2024: 33 · 2023: 37 · 2022: 39 · 2021: 51 · 2020: 59 · 2019: 41 · 2018: 50 · 2017: 52 · 2016: 67 · 2015: 64 · 2014: 63 · 2013: 64 · 2012: 45
- FWCI
- 38.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- U.S. Public Health Service (R01M56538-01)
- National Institute of Mental Health
- National Center for Research Resources (RR-0016)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD 33438)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- social memory, oxytocin, vasopressin, social recognition, social amnesia, oxytocin antagonist, spatial memory, behavioral inhibition, social behavior
- MeSH terms
- Amnesia, Retrograde, Animals, Behavior, Animal, Female, Male, Mice, Inbred C57BL, Olfactory Bulb, Oxytocin, Sexual Behavior, Animal, Social Behavior, Task Performance and Analysis, Mice, Knockout, Mice
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