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Cited by 39Neuroendocrine regulation and behaviorNeurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology Research

Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles

Open access
Borie, Amélie M., Agezo, Sena, Lunsford, Parker, Boender, Arjen J., Guo, Ji-Dong, Zhu, Hong, Berman, Gordon J., Young, Larry J. +1 more·2022·Current Biology
DOI 10.1016/j.cub.2022.01.014PMC PMC8930613

Published version of a preprint

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Abstract

Social relationships are dynamic and evolve with shared and personal experiences. Whether the functional role of social neuromodulators also evolves with experience to shape the trajectory of relationships is unknown. We utilized pair bonding in the socially monogamous prairie vole as an example of socio-sexual experience that dramatically alters behaviors displayed toward other individuals. We investigated oxytocin-dependent modulation of excitatory synaptic transmission in the nucleus accumbens as a function of pair-bonding status. We found that an oxytocin receptor agonist decreases the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in sexually naive virgin, but not pair-bonded, female voles, while it increases the amplitude of electrically evoked EPSCs in paired voles, but not in virgins. This oxytocin-induced potentiation of synaptic transmission relies on the de novo coupling between oxytocin receptor signaling and endocannabinoid receptor type 1 (CB1) receptor signaling in pair-bonded voles. Blocking CB1 receptors after pair-bond formation increases the occurrence of a specific form of social rejection-defensive upright response-that is displayed toward the partner, but not toward a novel individual. Altogether, our results demonstrate that oxytocin's action in the nucleus accumbens is changed through social experience in a way that regulates the trajectory of social interactions as the relationship with the partner unfolds, potentially promoting the maintenance of a pair bond by inhibiting aggressive responses. These results provide a mechanism by which social experience and context shift oxytocinergic signaling to impact neural and behavioral responses to social cues.

AI snapshot

Written from the paper’s full text.

TL;DR

Social experience changes how oxytocin modulates excitatory transmission in the female prairie vole nucleus accumbens: an OXTR agonist decreases spontaneous EPSC amplitude in virgins but potentiates evoked glutamatergic transmission in pair-bonded females via OXTR–CB1 endocannabinoid coupling. Blocking CB1 after pair bonding selectively increases partner-directed defensive upright behavior, suggesting this mechanism helps maintain the bond by reducing rejection of the partner.

Key findings

  • TGOT (10−7 M) decreased spontaneous EPSC amplitude in sexually naive virgin females but not in pair-bonded females, while it potentiated electrically evoked EPSCs/eEPSPf in paired females but not virgins.
  • The TGOT-induced potentiation in paired females required NAc OXTR and CB1 receptor activation: CRISPR/Cas9 OXTR knockdown reduced the eEPSPf potentiation, and the CB1 antagonist AM4113 (10−6 M) prevented both the potentiation and the TGOT-induced PPR correlation.
  • Pair bonding appeared to couple OXTR signaling to an existing eCB potentiation: the CB1 agonist ACEA potentiated eEPSPf in virgins and paired females, and ACEA’s effect in virgins was comparable in amplitude to TGOT’s effect in paired females.
  • In pair-bonded females, intra-NAc AM4113 increased defensive upright responses toward the partner to about twice vehicle levels, without affecting responses to a stranger; vehicle-treated females showed more defensive upright toward stranger than partner (Wilcoxon signed rank, p=0.0098 for vehicle, p=0.95 for AM4113).

Methods

  • Ovariectomized female prairie voles (2–6 months old) were cohabitated for 24 h with either a same-sex littermate (Virgin) or a male (Paired), then NAc core medium spiny neurons were studied with whole-cell and field slice electrophysiology.
  • Pharmacology included bath-applied TGOT, AM4113, DNQX, and ACEA; AAV-mediated CRISPR/Cas9 was used for unilateral NAc OXTR knockdown with contralateral LacZ control, verified by 125I-OVTA autoradiography.
  • Behavior included social preference tests and intruder tests after bilateral NAc cannula infusion of AM4113 or vehicle; data are means ± SEM, analyzed with factorial ANOVA followed by Sidak post hoc tests, α = 0.05, using GraphPad Prism 9.

Limitations

  • The paper states that fixed rather than random presentation order in the intruder tests precludes a rigorous conclusion about AM4113’s effects in stranger versus partner contexts.
  • The paper states that for the behavior–physiology correlation in Figure 2G, technical issues reduced the data available, and only animals showing a partner preference (9/15) were considered; it also notes that eCB involvement was not investigated in virgins because there was no systematic modulation in that group.
  • Evident from the text: findings are limited to female prairie voles that were ovariectomized and estradiol-primed, with in vitro slice electrophysiology and local pharmacology; the text does not report full sample sizes for every experiment in the main narrative.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.cub.2022.01.014

Cites

87 of 87 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 43 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    In virgin female prairie voles, TGOT does not increase the amplitude of electrically evoked EPSCs in nucleus accumbens core medium spiny neurons.

    “while it increases the amplitude of electrically evoked EPSCs in paired voles, but not in virgins”
    • Also stated in: § Across individuals, the amplitude of TGOT-induced potentiation depends on socio-sexual experience · plain
      “whereas in Virgin females it remained unchanged (Figure 2F)”
    Quote in the paperSubstantial claim
  • Findingown data

    In pair-bonded female prairie voles, the amplitude of the TGOT-induced potentiation of the field eEPSP correlates with the strength of partner preference.

    “specifically for partner-preferring Paired females, the amplitude of the field response correlated with our measure for partner preference, defined as the fraction of time spent near the partner relative to the total time spent near either animal during the second SPT (Figure 2G).”
    Quote in the paperSubstantial claim
  • Findingown data

    TGOT does not influence the frequency of spontaneous EPSCs in either virgin or pair-bonded female prairie voles.

    “TGOT did not influence the frequency of spontaneous Excitatory PostSynaptic Currents (sEPSC) in either Virgin or Paired females (Figure 1B).”
    Quote in the paperSubstantial claim
  • Findingown data

    In sexually naive virgin female prairie voles, the oxytocin receptor agonist TGOT decreases the amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) in nucleus accumbens core medium spiny neurons.

    “We found that an oxytocin receptor agonist decreases the amplitude of spontaneous Excitatory Postsynaptic Currents (EPSCs) in sexually naive virgin, but not pair-bonded, female voles”
    • Also stated in: § The effect of an OXTR agonist on spontaneous and evoked synaptic activity depends on social experience · plain
      “TGOT induced a significant decrease of the sEPSCs amplitude in Virgin but not in Paired females (Figure 1C–D)”
    Quote in the paperSubstantial claim
  • Findingown data

    In pair-bonded female prairie voles, TGOT increases the amplitude of electrically evoked EPSCs in nucleus accumbens core medium spiny neurons.

    “while it increases the amplitude of electrically evoked EPSCs in paired voles, but not in virgins”
    • Also stated in: § The effect of an OXTR agonist on spontaneous and evoked synaptic activity depends on social experience · plain
      “TGOT produced a more potentiated response in Paired compared to Virgin females (Figure 1G)”
    • Also stated in: § Across individuals, the amplitude of TGOT-induced potentiation depends on socio-sexual experience · plain
      “the amplitude of the eEPSPf was significantly increased following TGOT application in Paired females”
    Quote in the paperSubstantial claim
  • May combine two claims. 19
  • Classified as probably not a substantial claim. 17

  • May combine two claims.

    Findingown data

    In pair-bonded female prairie voles, vehicle-treated animals spent more time in defensive upright against the stranger than against their partner, while AM4113-treated animals did not.

    “vehicle (but not AM4113) treated animals spent more time in the defensive upright position against the stranger than against their partner (Wilcoxon signed rank, p=0.0098 for vehicle, p=0.95 for AM4113)”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In pair-bonded female prairie voles, blocking CB1 receptors in the nucleus accumbens increases the occurrence of defensive upright response toward the partner but not toward a novel individual.

    “Blocking CB1 receptors after pair bond formation increases the occurrence of a specific form of social rejection – defensive upright response – that is displayed towards the partner but not towards a novel individual.”
    • Also stated in: § Blocking CB1 receptor activation in the NAc of Paired females selectively increases partner rejection · plain
      “animals given AM4113 spent about twice as much time in a defensive upright posture when the partner was present, as compared to vehicle treated animals (Figure 5G)”
    • Also stated in: § Blocking CB1 receptor activation in the NAc of Paired females selectively increases partner rejection · plain
      “females showed similar rejection responses towards the stranger irrespective of the modulation of the eCB system (Figure 5F).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Even in virgin animals, TGOT significantly decreases the paired pulse ratio, but this change is not correlated to the change in EPSC amplitude.

    “Notably, even in virgin animals, TGOT significantly decreases the PPR (data not shown) but, this change is not correlated to the change in EPSC amplitude, suggesting the lack of a consistent relationship with the strength of glutamatergic synaptic transmission.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationcitation

    Oxytocin and reward systems are involved in various types of social relationships and social-decision making in a large range of species, suggesting that the findings of this paper may not be limited to pair bonding.

    “Importantly, oxytocin and the reward systems are involved in various types of social relationships and social-decision making in a large range of species 69,70, suggesting that the findings of this paper may not be limited to pair bonding.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [69] De Dreu, 2016, Oxytocin conditions intergroup relations Through upregulated in-group empathy, cooperation, conformity, and defense, Biol. Psychiatry source

      Not checked in the free run.

    • cites [70] Nagasawa, 2021, Neuroendocrine mechanisms of social bonds and separation stress in rodents, dogs, and other species, Curr. Top. Behav. Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    In paired prairie voles, OXTR agonists act on receptors located on nucleus accumbens cells and trigger an eCB-mediated synaptic potentiation involving a putative presynaptic mechanism.

    “In paired prairie voles, they act on receptors located on NAc cells and trigger an eCB-mediated synaptic potentiation involving a putative presynaptic mechanism.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The socio-sexual experience-contingent eCB-dependent oxytocinergic potentiation of NAc MSNs could influence the trajectory of social behavior and promote the expression of a bond.

    “Hence, the socio-sexual experience-contingent eCB-dependent oxytocinergic potentiation of NAc MSNs described here could influence the trajectory of social behavior and promote the expression of a bond.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The physiological effect of an OXT-eCB-based potentiation could allow context-dependent, upstream inputs to gain enhanced salience by amplifying excitatory transmission.

    “The physiological effect of an OXT-eCB-based potentiation could allow context-dependent, upstream inputs to gain enhanced salience by amplifying excitatory transmission.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The effect of intranasal OXT depends on the partner status of the subject: it keeps men in a monogamous relationship from being too close to a new woman without affecting single men.

    “Indeed, the effect of intranasal OXT depends on the partner status of the subject: it keeps men in a monogamous relationship from being too close to a new woman without affecting single men 77.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [77] Scheele, 2012, Oxytocin modulates social distance between males and females, J. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In virgins, social interactions facilitating future pair bonding (e.g. mating) would release OXT, resulting in decreased amplitude of sEPSCs in NAc MSNs, which may serve to decrease noise, facilitating linking the cues of the future partner with the reward system.

    “In virgins, social interactions facilitating future pair bonding (e.g. mating), would release OXT, resulting in decreased amplitude of sEPSCs in NAc MSNs, which may serve to decrease noise, facilitating linking the cues of the future partner with the reward system 2 (Figure 6 left).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [2] Walum, 2018, The neural mechanisms and circuitry of the pair bond, Nat. Rev. Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The electrophysiological effect of OXTR agonist application depends on social experience, with a potentiation of excitation mediated through a coupling between OXTR and CB1 receptor activation emerging in paired animals.

    “We found that the electrophysiological effect of OXTR agonist application depends on social experience, with a potentiation of excitation mediated through a coupling between OXTR and CB1 receptor activation emerging in paired animals.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Prairie voles form a lifelong pair bond upon social interaction and mating, resulting in a dramatic change in the way they interact with other individuals.

    “Upon social interaction and mating, prairie voles (Microtus ochrogaster) form a lifelong pair bond resulting in a dramatic change in the way they interact with other individuals 22.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [22] McGraw, 2010, The prairie vole: an emerging model organism for understanding the social brain, Trends Neurosci source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prairie voles and other monogamous species express high levels of oxytocin receptors in the nucleus accumbens while non-monogamous species do not.

    “Prairie voles and other monogamous species, including marmosets and humans express high levels of oxytocin receptors (OXTR) in the NAc while non-monogamous species, such as laboratory mice and rhesus macaques, do not 24–26.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [24] Young, 2021, On the origins of diversity in social behavior, Jpn. J. Anim. Psychol. source

      Not checked in the free run.

    • cites [25] Freeman, 2016, Comparative perspectives on oxytocin and vasopressin receptor research in rodents and Primates: translational implications, J. Neuroendocrinol. source

      Not checked in the free run.

    • cites [26] Bethlehem, 2017, Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women, Transl. Psychiatry source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    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.”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [14] Ferguson, 2001, Oxytocin in the medial amygdala is essential for social recognition in the mouse, J. Neurosci. source

      Not checked in the free run.

    • cites [15] Lukas, 2013, Oxytocin mediates rodent social memory within the lateral septum and the medial amygdala depending on the relevance of the social stimulus: male juvenile versus female adult conspecifics, Psychoneuroendocrinology source

      Not checked in the free run.

    • cites [2] Walum, 2018, The neural mechanisms and circuitry of the pair bond, Nat. Rev. Neurosci. source

      Not checked in the free run.

    • cites [16] Marlin, 2015, Oxytocin enables maternal behaviour by balancing cortical inhibition, Nature source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OXT increases the perceived attractiveness of one's partner but not of other women.

    “it increases the perceived attractiveness of one’s partner but not of other women78.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [78] Scheele, 2013, Oxytocin enhances brain reward system responses in men viewing the face of their female partner, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable).

    Premisecitation

    Social relationships evolve over time through interactions that reshape how one perceives, engages with, and feels about another individual.

    “Social relationships evolve over time through interactions – both positive and negative – that reshape how one subsequently perceives 1, engages with 2 and feels 3 about another individual.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [1] Suvilehto, 2015, Topography of social touching depends on emotional bonds between humans, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

    • cites [2] Walum, 2018, The neural mechanisms and circuitry of the pair bond, Nat. Rev. Neurosci. source

      Not checked in the free run.

    • cites [3] Whitehouse, 2014, Brothers in arms: Libyan revolutionaries bond like family, Proc. Natl. Acad. Sci. USA source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    OXT action results in modulation of neuronal activity in brain areas regulating social behaviors to increase the salience and reinforcing value of social stimuli.

    “OXT action results in modulation of neuronal activity in brain areas regulating social behaviors 17 to increase the salience and reinforcing value of social stimuli 18,19.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [17] Johnson, 2017, Oxytocin receptors modulate a social salience neural network in male prairie voles, Horm. Behav. source

      Not checked in the free run.

    • cites [18] Young, 2015, Oxytocin, social cognition and psychiatry, Neuropsychopharmacology source

      Not checked in the free run.

    • cites [19] Shamay-Tsoory, 2016, The social salience hypothesis of oxytocin, Biol. Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    OXT neurons are activated in response to social stimuli including social touch, infant cries and mating.

    “Furthermore, OXT neurons are activated in response to social stimuli including social touch 20, infant cries 21 and mating.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [20] Tang, 2020, Social touch promotes interfemale communication via activation of parvocellular oxytocin neurons, Nat. Neurosci. source

      Not checked in the free run.

    • cites [21] Valtcheva, 2021, Neural circuitry for maternal oxytocin release induced by infant cries, bioRxiv

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Oxytocin is a key neuromodulator for the regulation of social behaviors and a target for treatment of neuropsychiatric disorders.

    “Oxytocin (OXT) is a key neuromodulator for the regulation of social behaviors 9,10, and a target for the treatment of neuropsychiatric disorders 11–13.”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [9] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu. Rev. Neurosci. source

      Not checked in the free run.

    • cites [10] Johnson, 2017, Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience, Neurosci. Biobehav. Rev. source

      Not checked in the free run.

    • cites [11] Meyer-Lindenberg, 2011, Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine, Nat. Rev. Neurosci. source

      Not checked in the free run.

    • cites [12] DeMayo, 2019, Circuits for social learning: a unified model and application to autism spectrum disorder, Neurosci. Biobehav. Rev. source

      Not checked in the free run.

    • cites [13] Ford, 2021, Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry, Curr. Opin. Neurobiol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pair-bonding depends on the duration of cohabitation and constitutes a shift over time in the behavioral repertoire of adult animals.

    “Indeed, pair-bonding depends on the duration of cohabitation and constitutes a shift over time in the behavioral repertoire of adult animals 4.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [4] Amadei, 2017, Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles, Nature source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductown data

    In slice electrophysiology experiments, OXT concentration and presynaptic stimulation intensity were controlled.

    “Importantly, in our slice electrophysiology experiments, we controlled for both OXT concentration and presynaptic stimulation intensity.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Affiliative and aggressive/defensive behaviors were scored blind to treatment group.

    “Affiliative and aggressive/defensive behaviors were scored blind to treatment group.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Neuromodulators are well documented to act centrally in the brain to modulate social behaviors.

    “although neuromodulators are well documented to act centrally in the brain to modulate social behaviors 6–8”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [6] Miranda, 2009, Dissecting natural sensory plasticity: hormones and experience in a maternal context, Hear. Res. source

      Not checked in the free run.

    • cites [7] Banerjee, 2013, Storing maternal memories: hypothesizing an interaction of experience and estrogen on sensory cortical plasticity to learn infant cues, Front. Neuroendocrinol. source

      Not checked in the free run.

    • cites [8] Donaldson, 2008, Oxytocin, vasopressin, and the neurogenetics of sociality, Science source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Pair-bonds depend on the extent and nature of social interactions, can be broken, reformed with new individuals, and are dynamic.

    “Pair-bonds depend on the extent and nature of the social interactions 67, can be broken, as well as reformed with new individuals, and are thus dynamic 68.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [67] Williams, 1992, Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience, Horm. Behav. source

      Not checked in the free run.

    • cites [68] Sadino, 2021, Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles, bioRxiv

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Pair bonding in voles involves cognitive resources to associate cues from the partner with the reward system, and leads to a dramatic change of behavior displayed both in the presence of the partner and novel conspecifics.

    “Rather than being a deterministic program in these animals, pair bonding in voles involves cognitive resources to associate cues from the partner with the reward system, and leads to a dramatic change of the behavior displayed both in the presence of the partner and novel conspecifics.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductreasoning

    Recordings from fast spiking interneurons were excluded based on their electrophysiological properties, so results were obtained exclusively from MSNs.

    “Recordings from fast spiking interneurons were excluded based on their electrophysiological properties so that the results presented here were obtained exclusively from MSNs.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Unless otherwise noted, all available data was used for all figures.

    “Unless otherwise noted, for all figures, all available data was used.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationreasoning

    Alterations in the described mechanism could negatively affect the trajectory of relationships.

    “alterations in the described mechanism could negatively affect the trajectory of relationships.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Positions of cannulas were verified post mortem.

    “Positions of cannulas were verified post mortem.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisecitation

    24 h cohabitation with a male induces a strong pair bond as indicated by more time spent huddling with the partner compared to the stranger in a partner preference test.

    “Previous studies showed that 24 h cohabitation with a male induces a strong pair bond as indicated by more time spent huddling with the partner compared to the stranger in a partner preference test 67.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Williams, 1992, Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience, Horm. Behav. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    For the correlation in Fig. 2G, only animals presenting a preference for the partner (9/15) were considered.

    “Furthermore, for this figure, only animals presenting a preference for the partner (9/15) were considered.”
    Quote in the paperNot a substantial claim
30 of 30

  • The paper relies on this without support.

    Whether the functional role of social neuromodulators evolves with experience to shape the trajectory of relationships is unknown.

    “Whether the functional role of social neuromodulators also evolves with experience to shape the trajectory of relationships is unknown.”

  • The paper relies on this without support.

    The brain mechanisms acting when relationships are formed and expressed are likely to change over the course of subsequent encounters between two individuals.

    “Thus, the brain mechanisms acting when relationships are formed and expressed are likely to change over the course of subsequent encounters between two individuals.”

  • The paper relies on this without support.

    Much less is known about what modulates the expression or maintenance of social relationships.

    “much less is known about what modulates their expression or maintenance.”

  • The authors state this as an assumption.

    For interactions with the partner but not a novel male, OXTR activation triggers the local production of anandamide, a potent agonist of CB1 receptors.

    “We presume that for interactions with the partner but not novel male, OXTR activation triggers the local production of anandamide, a potent agonist of CB1 receptors.”
4 of 4

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In virgin female prairie voles, OXTR signaling, mimicking the first mating, decreases spontaneous activity of nucleus accumbens neurons, effectively reducing the noise in the circuit, perhaps to facilitate synaptic plasticity to make partner cues rewarding.

    “In virgin female prairie voles, OXTR signaling, mimicking the first mating, decreases spontaneous activity of NAcc neurons, effectively reducing the noise in the circuit, perhaps to facilitate synaptic plasticity to make partner cues rewarding.”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [140]

  • The oxytocin fibers in the nucleus accumbens originate from the paraventricular nucleus, and oxytocin is released in females during mating.

    “The OXT fibers in the NAcc originate from the PVN (140), and OXT is released in females during mating (141).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [140]

  • After pair bonding, OXTR signaling increases evoked nucleus accumbens cell activity from neural inputs, perhaps amplifying the signal of the neural representation of the partner, making the partner reinforcing and motivating affiliation.

    “After pair bonding, OXTR signaling increases evoked NAcc cell activity from neural inputs, perhaps amplifying the signal of the neural representation of the partner, making the partner reinforcing and motivating affiliation (140).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [140]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • NAc cannula coordinates use centimeters rather than millimeters

    Minor

    Both procedures say they target the NAc core, but the cannula coordinates put it 1.5 cm lateral and 4.3 cm deep, versus 2.6 mm lateral and 4.5 mm deep for the virus injection. The centimeter values differ by roughly an order of magnitude and are inconsistent with the stated target.

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Authors
Borie, A. M., Agezo, S., Lunsford, P., Boender, A. J., Guo, J.-D., Zhu, H., Berman, G. J., Young, L. J., & Liu, R. C.
Affiliations
  • Emory University (US)
  • University of Tsukuba (JP)
Corresponding author
  • Young, Larry J.
  • Liu, Robert C.
ORCID
Venue
Current Biology
Publisher
Elsevier BV
Published
2022-03
Volume
32
Issue
5
Pages
1026-1037.e4
ISSN
0960-9822 (ISSN-L)
DOI
10.1016/j.cub.2022.01.014
PMC
PMC8930613
OpenAlex
W4220941882
Cited by
39
References
87
Citations by year
2026: 2 · 2025: 14 · 2024: 10 · 2023: 4 · 2022: 9
FWCI
8.73
Type
journal article
Language
en
Open access
Licence
Locations
  • Current Biology (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • SSRN Electronic Journal (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health (P50MH100023, P51OD11132, R01MH115831)
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 › Neuroscience and Neuropharmacology Research
Keywords
oxytocin, nucleus accumbens, pair bonding, Microtus ochrogaster, social experience, synaptic transmission, excitatory postsynaptic currents, social rejection, social aggression
MeSH terms
Animals, Arvicolinae, Female, Humans, Nucleus Accumbens, Oxytocin, Pair Bond, Social Behavior, Receptors, Oxytocin, Grassland

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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