Oxytocin in the Medial Amygdala is Essential for Social Recognition in the Mouse
Open accessAbstract
Oxytocin (OT) knock-out mice fail to recognize familiar conspecifics after repeated social exposures, despite normal olfactory and spatial learning abilities. OT treatment fully restores social recognition. Here we demonstrate that OT acts in the medial amygdala during the initial exposure to facilitate social recognition. OT given before, but not after, the initial encounter restores social recognition in OT knock-out mice. Using c-Fos immunoreactivity (Fos-IR) as a marker of neuronal activation in this initial encounter, we found similar neuronal activation in the wild-type (WT) and OT knock-out mouse in olfactory bulbs, piriform cortex, cortical amygdala, and the lateral septum. Wild-type, but not OT knock-out mice exhibited an induction of Fos-IR in the medial amygdala. Projections sites of the medial amygdala also failed to show a Fos-IR induction in the OT knock-out mice. OT knock-out, but not WT, mice showed dramatic increases in Fos-IR in the somatosensory cortex and the hippocampus, suggesting alternative processing of social cues in these animals. With site-specific injections of OT and an OT antagonist, we demonstrate that OT receptor activation in the medial amygdala is both necessary and sufficient for social recognition in the mouse.
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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 [36]
A single treatment with oxytocin 24 hours after birth alters the expression of alloparental behavior in female prairie voles when they reach adulthood.
“For example, a single treatment with OT 24 hours after birth alters the expression of alloparental behavior in female prairie voles when they reach adulthood [46].”
From Oxytocin and the Neural Mechanisms Regulating Social Cognition and Affiliative Behavior (2009) · cites this paper as [46]
The Animals and Social recognition tests sections describe male mice tested for social recognition, with adult females used as stimulus animals. Searches for neonatal oxytocin treatment and alloparental behavior in female prairie voles found no passage addressing the claimed result. (LLM, conf=0.76)
Experimental — accuracy not yet measuredOTR knockout mice show social recognition deficits that can be remediated by oxytocin injections in medial amygdala.
“OTR mouse knockouts show social recognition deficits that can be remediated by oxytocin injections in the medial amygdala [163].”
From Consensus Paper: Pathological Role of the Cerebellum in Autism (2012) · cites this paper as [163]
Infusion of an oxytocin receptor antagonist into the medial amygdala of wild-type mice recapitulates social memory deficits.
“and infusions of an OXTR antagonist into the MeA of wild-type mice recapitulates those deficits in social memory (24).”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [24]
Infusion of oxytocin directly into the medial amygdala of oxytocin knockout mice rescues social amnesia.
“Infusions of OT directly into the medial amygdala (MeA) of OT knockout mice rescues the social amnesia described above”
From Comparative Perspectives on Oxytocin and Vasopressin Receptor Research in Rodents and Primates: Translational Implications (2016) · cites this paper as [24]
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 [24]
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 2001
Oxytocin activity in the septum and amygdala is required for social memory.
“Utilizing the three-chamber social memory assay in rodents, it was found that OXT activity in the septum and amygdala is required for social memory [43,70].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [43]
Mice with impairments in either the oxytocin or vasopressin system show deficits in distinguishing between familiar and novel conspecifics.
“For example, mice with impairments in either system show deficits in distinguishing between familiar and novel conspecifics (74,94,95).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [74]
OXTRs in the medial amygdala receive oxytocin input from the paraventricular nucleus that help discriminate between sex and individual cues.
“OXTRs in the MeA receive OXT input from the PVN that help discriminate between sexand individual cues (53,74,96).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [74]
OXT is released within the brain as relationships form and facilitates experience-dependent social adaptations including formation of social memories, establishment of mating-induced pair bonds, and maternal responsiveness.
“OXT is released within the brain as relationships form and it facilitates experience-dependent social adaptations including the formation of social memories 14,15, the establishment of mating-induced pair bonds 2 and maternal responsiveness 16.”
From Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles (2022) · cites this paper as [14]
OT acts in the medial amygdala during initial exposure to other conspecifics to facilitate social recognition.
“In a subsequent study (Ferguson et al. 2001), we found that OT acts in the medial amygdala during initial exposure to other conspecifics to facilitate social recognition.”
From A precision medicine approach to oxytocin trials (2017) · cites this paper as Ferguson et al. 2001
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., 2001
The neuropeptide oxytocin (OT) is implicated in the modulation of many social responses.
“The neuropeptide oxytocin (OT) is implicated in the modulation of many social responses (Ross and Young, 2009; Insel and Hulihan, 1995; Ferguson et al., 2001; Dölen et al., 2013).”
From Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice (2017) · cites this paper as Ferguson et al., 2001
Considering the expression of OXTR in the MeApd, and its role in social and sexual recognition, plasticity may be also directly derived from the regulation of local circuitry in the MeA.
“Considering the expression of OXTR in the MeApd, and its role in social and sexual recognition (Ferguson et al., 2001; Yao et al., 2017), plasticity may be also directly derived from the regulation of local circuitry in the MeA.”
From Neuronal Representation of Social Information in the Medial Amygdala of Awake Behaving Mice (2017) · cites this paper as Ferguson et al., 2001
Intranasal oxytocin enhances prosocial and affiliative behaviors in rodents and non-human primates.
“Intranasal oxytocin is also known to enhance prosocial and affiliative behaviors in rodents (Ferguson et al., 2001; Witt et al., 1992) and non-human primates (Chang and Platt, 2013).”
From Effects of adverse childhood experiences on the association between intranasal oxytocin and social stress reactivity among individuals with cocaine dependence (2015) · cites this paper as Ferguson et al., 2001
Oxytocin can specifically affect social behaviors, suggesting separable mechanisms at the pharmacological level.
“Other studies, however, have suggested that the neuropeptide oxytocin can specifically affect social behaviors, which would suggest separable mechanisms at the pharmacological level.”
From Oxytocin decreases aversion to angry faces in an associative learning task (2010) · cites this paper as Ferguson et al., 2001
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“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).”
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“For example, OXT receptor knockout mice demonstrate several aberrations in social behavior, including aggression and mother-offspring interaction (Nishimori et al., 2008) that can be fully restored by injection of OXT (Ferguson et al., 2001).”
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- Authors
- Ferguson, J. N., Aldag, J. M., Insel, T. R., & Young, L. J.
- Affiliations
- Emory University (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2001-10-15
- Volume
- 21
- Issue
- 20
- Pages
- 8278-8285
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6763861
- OpenAlex
- W2164671673
- Cited by
- 1,043
- References
- 56
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 29 · 2023: 43 · 2022: 46 · 2021: 61 · 2020: 30 · 2019: 37 · 2018: 63 · 2017: 48 · 2016: 61 · 2015: 78 · 2014: 53 · 2013: 53 · 2012: 59
- FWCI
- 38.87
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Neuroscience (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (9876754)
- National Institute of Mental Health (R29MH056897, MH 56897, R01MH056897)
- 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
- oxytocin, medial amygdala, social recognition, oxytocin receptor, c-Fos neuronal activation, olfactory bulb, piriform cortex, cortical amygdala, lateral septum, somatosensory cortex, hippocampus, social behavior
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Dose-Response Relationship, Drug, Female, Immunohistochemistry, Injections, Intraventricular, Male, Mice, Inbred Strains, Olfactory Bulb, Ovariectomy, Oxytocin, Smell, Social Behavior, Proto-Oncogene Proteins c-fos, Mice, Knockout, Recognition, Psychology, Mice
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