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Cited by 191Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities

Open access
Rigney, Nicole, de Vries, Geert J, Petrulis, Aras, Young, Larry J·2022·Endocrinology
DOI 10.1210/endocr/bqac111PMC PMC9337272
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Abstract

Oxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively. However, both peptides are also released in the brain, where they modulate several aspects of social behaviors. Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli. Vasopressin modulates social communication, social investigation, territorial behavior, and aggression, predominantly in males. Both peptides facilitate social memory and pair bonding behaviors in monogamous species. Here we review the latest research delineating the neural circuitry of the brain oxytocin and vasopressin systems and summarize recent investigations into the circuit-based mechanisms modulating social behaviors. We highlight research using modern molecular genetic technologies to map, monitor activity of, or manipulate neuropeptide circuits. Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed. We conclude with a discussion of the translational implications of oxytocin and vasopressin for improving social functioning in disorders with social impairments, such as autism spectrum disorder.

AI snapshot

Written from the paper’s full text.

TL;DR

This mini-review summarizes how brain oxytocin (OXT) and vasopressin (AVP) systems regulate social behavior through defined neural circuits, with OXT promoting maternal nurturing, bonding, social reward, and social salience, while AVP modulates social communication, investigation, territoriality, and aggression, predominantly in males. It highlights recent molecular-genetic circuit studies and discusses translational opportunities for social impairments such as autism spectrum disorder (ASD).

Key findings

  • OXT acts through one canonical receptor (OXTR), whereas AVP acts through V1aR, V1bR, and V2; behavioral AVP effects are mediated primarily by V1aR and V1bR, while V2 regulates fluid homeostasis in the kidney.
  • BNST/MeA AVP cells are steroid-dependent and sexually dimorphic: male rodents have 2 to 3 times as many AVP cells as females in the BNST/MeA, with pronounced sex-different projections to social-behavior areas; PVN AVP projections are generally denser in female than male mice.
  • Circuit-specific manipulations show PVN OXT projections to nucleus accumbens and dorsal raphe serotonin systems are required for social reward, PVN OXT to VTA increases social investigation, PVN AVP input to hippocampal CA2 enhances social memory via V1bR, and BNST AVP cell ablation impairs male social recognition and reduces male-male social investigation.
  • Translational evidence is mixed: intranasal OXT efficacy has been mixed, the V1aR antagonist balovaptan showed mixed effects on social endpoints in ASD trials, while intranasal AVP improved social abilities in children with ASD and decreased cerebrospinal fluid AVP has been reported in ASD and in socially impaired male rhesus macaques.

Methods

  • Narrative mini-review of recent research on behaviorally relevant sources, inputs, outputs, and receptor systems of brain OXT and AVP circuits; no new data were generated or analyzed, per the Data availability statement.
  • Synthesizes studies using modern molecular genetic technologies, including Cre recombinase lines, conditional knockout, viral tracing, optogenetics, chemogenetics, knockdown/overexpression, CRISPR editing, electrophysiology, and transcriptomics, across rodents, prairie voles, medaka fish, zebrafish, nonhuman primates, and humans.
  • No systematic search strategy, inclusion criteria, or meta-analysis is described.

Limitations

  • The paper states that research has disproportionately focused on OXT over AVP and calls for rebalancing OXT/AVP research, especially to refine different AVP circuits in social behavior.
  • The paper states that more neuroanatomical experiments are needed to map OXT/AVP cells in the extended amygdala, that sources of AVP regulating pair bonding and mate choice have not been explored, and that it remains unclear whether hypothalamic OXT/AVP release is synchronized across sources or region-specific.
  • The paper notes that laboratory mice have limited behavioral diversity and that species differences in OXT/AVP receptor distributions are well documented, requiring expanded tools in other species; evident from the text, as a mini-review it provides no primary data and its translational claims rest on mixed clinical trial results.

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

Integrity signals

Registry

Crossref · 10.1210/endocr/bqac111

Cites

173 of 173 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 216 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Central vasopressin regulates social communication, territorial aggression, pair bonding, and mate guarding, especially in males.

    “whereas central AVP has been shown to regulate social communication, territorial aggression, pair bonding, and mate guarding, especially in males (9,15,16).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [9] Walum, 2018, The neural mechanisms and circuitry of the pair bond, Nat Rev Neurosci. source

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    • cites [15] Nair, 2006, Vasopressin and pair-bond formation: genes to brain to behavior, Physiology (Bethesda).

      Not checked in the free run.

    • cites [16] Albers, 2015, Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network, Front Neuroendocrinol. source

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  • Premisenone given

    The paraventricular and supraoptic nuclei of the hypothalamus release oxytocin and vasopressin both centrally and peripherally.

    “The paraventricular (PVN) and supraoptic nuclei (SON) of the hypothalamus release OXT and AVP, both centrally and peripherally.”
    Quote in the paperNot a substantial claim
  • Premisecitation

    Species differences in the distribution of oxytocin and vasopressin receptors are well documented.

    “Since laboratory mice have limited behavioral diversity, and species differences in the distribution of OXT/AVP receptors are well documented (10), it is important to expand these intersectional tools to other species (23).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu Rev Neurosci. source

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  • Premisecitation

    There is species diversity in oxytocin and vasopressin effects on social behaviors.

    “Species diversity in oxytocin and vasopressin effects on social behaviors are also discussed.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu Rev Neurosci. source

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    • cites [23] Boender, 2020, Oxytocin, vasopressin and social behavior in the age of genome editing: a comparative perspective, Horm Behav. source

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  • Premisecitation

    Oxytocin increases the salience of social stimuli.

    “Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [10] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu Rev Neurosci. source

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    • cites [78] Namba, 2016, Activation of arginine vasopressin receptor 1a facilitates the induction of long-term potentiation in the accessory olfactory bulb of male mice, Neurosci Lett. source

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  • Classified as probably not a substantial claim. 9

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    Premisecitation

    Oxytocin acting centrally is essential for maternal behavior, mother-infant bonding, sexual behavior, and other affiliative behaviors such as pair bonding and empathy-like consoling.

    “Since then, OXT acting centrally has been shown to be essential for maternal behavior, mother-infant bonding, sexual behavior, and other affiliative behaviors such as pair bonding and empathy-like consoling (8)(9)(10)(11)(12)(13)(14)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (8)(9)(10)(11)(12)(13)(14)

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    Premisecitation

    Vasopressin is also produced in the suprachiasmatic nucleus, which regulates circadian rhythms, and in the accessory nuclei/nucleus circularis region, a likely source of vasopressin regulating aggression and competitive communication.

    “AVP is also produced in other hypothalamic nuclei such as the suprachiasmatic nucleus, well known for regulating circadian rhythms (42), and the accessory nuclei/nucleus circularis region, a likely source of AVP regulating aggression and competitive communication (43).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [42] Rohr, 2021, Vasopressin regulates daily rhythms and circadian clock circuits in a manner influenced by sex, Horm Behav. source

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    • cites [43] Gobrogge, 2009, Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent, Proc Natl Acad Sci U S A. source

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    Premisecitation

    Oxytocin is also produced in the medial preoptic area, where it regulates maternal and sexual behavior.

    “OXT is also produced in the medial preoptic area (MPOA), where it regulates maternal and sexual behavior (44).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Jirikowski, 2019, Diversity of central oxytocinergic projections, Cell Tissue Res. source

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

    Premisecitation

    Oxytocin and vasopressin are peptide hormones secreted from the pituitary that have peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively.

    “Oxytocin and vasopressin are peptide hormones secreted from the pituitary that are well known for their peripheral endocrine effects on childbirth/nursing and blood pressure/urine concentration, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites (3)(4)(5)(6)

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    Premisecitation

    Oxytocin promotes maternal nurturing and bonding.

    “Oxytocin promotes maternal nurturing and bonding, enhances social reward, and increases the salience of social stimuli.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (8)(9)(10)(11)(12)(13)(14)

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    Premisenone given

    Both oxytocin and vasopressin are also released in the brain, where they modulate several aspects of social behaviors.

    “However, both peptides are also released in the brain, where they modulate several aspects of social behaviors.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Some behavioral effects of oxytocin and vasopressin are functionally linked to their peripheral function: oxytocin promotes birth and nursing but also parental nurturing, while vasopressin modulates urine production and also territorial behavior involving urine and scent marking.

    “Some of the behavioral effects of OXT and AVP are functionally linked to their peripheral function, as OXT promotes birth and nursing but also parental nurturing, while AVP modulates urine production and also territorial behavior, which often involves urine and scent marking (17,18).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [17] Arakawa, 2022, Exocrine scent marking: coordinative role of arginine vasopressin in the systemic regulation of social signaling behaviors, Neurosci Biobehav Rev. source

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    • cites [18] Rilling, 2014, The biology of mammalian parenting and its effect on offspring social development, Science. source

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    Premisecitation

    Some reports show greater vasopressin mRNA density in the supraoptic nucleus of male rats and greater oxytocin production in female mice, but other studies show similar amounts of oxytocin and vasopressin in both sexes in the paraventricular/supraoptic nuclei of various rodent species, nonhuman primates, and humans.

    “Some reports have shown that AVP messenger RNA (mRNA) density measurements in the SON of rats are greater in males (50), while, in mice, OXT production is greater in females (51); however, other studies have shown a similar amount of OXT and AVP in both sexes in the PVN/SON of various rodent species, nonhuman primates, and humans (49,52).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [50] Taylor, 2012, Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats, Biol Sex Differ. source

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    • cites [51] Häussler, 1990, Sex differences among oxytocin-immunoreactive neuronal systems in the mouse hypothalamus, J Chem Neuroanat.

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    • cites [49] Dumais, 2016, Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior, Front Neuroendocrinol. source

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    • cites [52] Rigney, 2021, Sex differences in the control of social investigation and anxiety by vasopressin cells of the paraventricular nucleus of the hypothalamus, Neuroendocrinology. source

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    Premisecitation

    The sex difference in vasopressin expression is driven primarily by organizational effects of steroid hormones, although hormone-independent influences of sex chromosomes play a role.

    “The sex difference in AVP expression is driven primarily by organizational effects of steroid hormones, although hormone-independent influences of sex chromosomes play a role (67).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [67] De Vries, 2002, A model system for study of sex chromosome effects on sexually dimorphic neural and behavioral traits, J Neurosci. source

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    Premisecitation

    Although the number of paraventricular vasopressin neurons does not appear to differ by sex, central projections from these neurons are generally denser in female than in male mice.

    “Although the number of PVN AVP neurons do not appear to differ by sex, central projections from these neurons are generally denser in female than in male mice (60).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [60] Rood, 2013, Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain, J Comp Neurol. source

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    Premisecitation

    The paraventricular and supraoptic nuclei contain magnocellular oxytocin and vasopressin neurosecretory cells that project to the posterior pituitary and release each peptide peripherally as a hormone; the paraventricular nucleus also contains nonneurosecretory parvocellular cells that modulate anterior pituitary adrenocorticotropin release and project to other brain and spinal cord areas.

    “Both the PVN and SON contain magnocellular OXT and AVP neurosecretory cells that project to the posterior pituitary, releasing each peptide peripherally as a hormone (45), and the PVN contains an additional population of nonneurosecretory, parvocellular cells that modulate anterior pituitary release of adrenocorticotropin (46), as well as project to other brain and spinal cord areas (47,48)”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [45] Scott Young, 2003, Transgenesis and the study of expression, cellular targeting and function of oxytocin, vasopressin and their receptors, Neuroendocrinology. source

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    • cites [46] Gillies, 1982, Corticotropin releasing activity of the new CRF is potentiated several times by vasopressin, Nature. source

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    • cites [47] Castel, 1988, The neurophysin-containing innervation of the forebrain of the mouse, Neuroscience. source

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    • cites [48] Ludwig, 2006, Dendritic peptide release and peptide-dependent behaviours, Nat Rev Neurosci. source

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  • May combine two claims.

    Premisenone given

    Oxytocin has one canonical receptor type (OXTR), whereas vasopressin has three: V1aR, V1bR, and V2.

    “OXT has one canonical receptor type (ie, OXTR), whereas AVP has 3: V1aR, V1bR, and V2.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin neurons in the bed nucleus of the stria terminalis of California mice make local connections within the bed nucleus of the stria terminalis, project to the hypothalamus, and are involved in social vigilance.

    “However, OXT neurons in the BNST of California mice make local connections within the BNST, project to the hypothalamus, and are involved in social vigilance (66).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [66] Duque-Wilckens, 2020, Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance, Proc Natl Acad Sci U S A. source

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    Premisecitation

    Supraoptic oxytocin-expressing cells have more restricted projections, mainly to the posterior pituitary, but also project to the medial and central amygdala.

    “The SON OXT-expressing cells have more restricted projections, mainly to the posterior pituitary, but also project to the medial and central amygdala (44).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Jirikowski, 2019, Diversity of central oxytocinergic projections, Cell Tissue Res. source

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    Interpretationcitation

    Few of the inputs to paraventricular vasopressin cells are vasopressin immunoreactive and may be oxytocinergic, suggesting functional crosstalk between oxytocin and vasopressin paraventricular cells.

    “Few of the inputs to PVN AVP cells are AVP immunoreactive, and may, in fact, be OXT-ergic (61,62), suggesting functional crosstalk between OXT and AVP PVN cells.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [61] Wei, 2021, Presynaptic inputs to vasopressin neurons in the hypothalamic supraoptic nucleus and paraventricular nucleus in mice, Exp Neurol. source

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    • cites [62] Kim, 2021, Neural basis for regulation of vasopressin secretion by anticipated disturbances in osmolality, Elife source

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    Interpretationcitation

    Humans, chimpanzees, and other nonhuman primate species all show unique distributions of OXTR and V1aR in the brain, which may relate to species differences in primate social behaviors.

    “Humans, chimpanzees, and other nonhuman primate species all show unique distributions of OXTR and V1aR in the brain, which may relate to species differences in primate social behaviors (70).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Rogers Flattery, 2022, Distribution of brain oxytocin and vasopressin V1a receptors in chimpanzees (Pan troglodytes): comparison with humans and other primate species, Brain Struct Funct. source

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    Interpretationcitation

    The distribution of OXTR messenger RNA in prairie vole brain is surprisingly widespread, suggesting that oxytocin may modulate essentially brain-wide circuit activity.

    “In addition, the distribution of OXTR messenger RNA in prairie vole brain is surprisingly widespread, suggesting that OXT may modulate essentially brain-wide circuit activity (71).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [71] Inoue, 2022, Oxytocin receptors are widely distributed in prairie vole (Microtus ochrogaster) brain: relation to social behavior, genetic polymorphisms, and the dopamine system, J Comp Neurol. source

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    Premisecitation

    While there is remarkable consistency in the distribution of oxytocin and vasopressin neurons and their projections across vertebrates, there are striking species differences in the distributions of oxytocin and vasopressin receptors in the brain, even between closely related species.

    “While there is remarkable consistency in the distribution of OXT and AVP neurons and their projections across vertebrates (33), there are striking species differences in the distributions in the distribution of OXT and AVP receptors in the brain, even between closely related species (10).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] De Vries, 2006, Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints, Neuroscience. source

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    • cites [10] Froemke, 2021, Oxytocin, neural plasticity, and social behavior, Annu Rev Neurosci. source

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  • May combine two claims.

    Premisecitation

    The behavioral effects of vasopressin are mediated primarily by V1aR and V1bR, while vasopressin acts on V2 to regulate fluid homeostasis in the kidney.

    “The behavioral effects of AVP are mediated primarily by V1aR (or Avpr1a) and V1bR (16,37,38,49,68), while AVP acts on V2 to regulate fluid homeostasis in the kidney (69).”
    Quote in the paperNot a substantial claim0 of 6 sources checked
    • cites [16] Albers, 2015, Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network, Front Neuroendocrinol. source

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    • cites [37] Smith, 2019, Comparing vasopressin and oxytocin fiber and receptor density patterns in the social behavior neural network: implications for cross-system signaling, Front Neuroendocrinol. source

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    • cites [38] Jurek, 2018, The oxytocin receptor: from intracellular signaling to behavior, Physiol Rev. source

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    • cites [49] Dumais, 2016, Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior, Front Neuroendocrinol. source

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    • cites [68] French, 2016, Neuropeptide diversity and the regulation of social behavior in New World primates, Front Neuroendocrinol. source

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    • cites [69] Juul, 2014, The physiological and pathophysiological functions of renal and extrarenal vasopressin V2 receptors, Am J Physiol Renal Physiol. source

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    Premisecitation

    Male rodents have 2 to 3 times as many vasopressin cells as females in the bed nucleus of the stria terminalis/medial amygdala and pronounced sex-different projections to areas involved in social behavior such as the ventral pallidum, lateral septum, lateral habenula, dorsal raphe, periaqueductal gray, and other forebrain areas.

    “For example, male rodents have 2 to 3 times as many AVP cells as females in the BNST/MeA and pronounced sex-different projections to areas involved in social behavior such as the ventral pallidum, lateral septum (LS), lateral habenula, dorsal raphe (DR), periaqueductal gray, as well as other forebrain areas (33, 60)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [33] De Vries, 2006, Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints, Neuroscience. source

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    • cites [60] Rood, 2013, Site of origin of and sex differences in the vasopressin innervation of the mouse (Mus musculus) brain, J Comp Neurol. source

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    Premisecitation

    Son et al. found no correlation between oxytocin neuronal projections and oxytocin receptor expression, consistent with paracrine signaling.

    “Recently, Son et al (59) found no correlation between OXT neuronal projections and OXTR expression, consistent with paracrine signaling.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Son, 2022, Whole-brain wiring diagram of oxytocin system in adult mice, J Neurosci. source

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    Premisecitation

    Paraventricular oxytocin-expressing cells send fibers to the supraoptic nucleus forming the neurohypophyseal tract, and also send projections to the thalamus, cortex, amygdala, striatum, and hippocampus.

    “Oxytocin PVN OXT-expressing cells send fibers to the SON forming the neurohypophyseal tract (44), and classical retrograde tracing and modern viral tracing strategies in rats and mice have shown that the PVN OXT-expressing cells also send projections to the thalamus, cortex, amygdala, striatum, and hippocampus (Fig. 1A (53)(54)(55).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [44] Jirikowski, 2019, Diversity of central oxytocinergic projections, Cell Tissue Res. source

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    • cites (53)(54)(55)

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    Premisecitation

    There is a sex-specific role of vasopressin in the regulation of social play behavior in juvenile rats, as blocking V1aR in the lateral septum increases social play behavior in males and decreases it in females.

    “There is also a sex-specific role of AVP in the regulation of social play behavior in juvenile rats, as blocking V1aR in the LS increases social play behavior in males and decreases it in females (49).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [49] Dumais, 2016, Vasopressin and oxytocin receptor systems in the brain: sex differences and sex-specific regulation of social behavior, Front Neuroendocrinol. source

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    Premisecitation

    In male and female Syrian hamsters, social interaction increases c-Fos expression in oxytocin-immunoreactive neurons in the paraventricular and supraoptic nuclei, while OXTRs in the ventral tegmental area mediate the rewarding properties of these social interactions.

    “In male and female Syrian hamsters, social interaction increases the amount of c-Fos expression (a marker for neural activity) in OXT-immunoreactive neurons in the PVN and SON, while OXTRs in the VTA mediate the rewarding properties of these social interactions (84).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [84] Borland, 2019, Sex-dependent regulation of social reward by oxytocin receptors in the ventral tegmental area, Neuropsychopharmacology. source

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    Premisecitation

    Paraventricular vasopressin cell ablation increased female social investigation, but does not alter investigation in males.

    “PVN AVP cell ablation increased female social investigation, but does not alter investigation in males (52,90,91).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [52] Rigney, 2021, Sex differences in the control of social investigation and anxiety by vasopressin cells of the paraventricular nucleus of the hypothalamus, Neuroendocrinology. source

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    • cites [90] Rigney, 2019, Sexually dimorphic vasopressin cells modulate social investigation and communication in sex-specific ways, eNeuro. source

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    • cites [91] Rigney, 2021, Knockdown of sexually differentiated vasopressin expression in the bed nucleus of the stria terminalis reduces social and sexual behavior in male, but not female, mice, J Neuroendocrinol.

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    Premisecitation

    Although constitutive knockout of oxytocin does not alter social approach in mice, specific oxytocin systems do influence social reward, approach, and investigation.

    “Although constitutive KO of OXT does not alter social approach in mice (79), specific OXT systems do influence social reward, approach, and investigation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [79] Crawley, 2007, Social approach behaviors in oxytocin knockout mice: comparison of two independent lines tested in different laboratory environments, Neuropeptides. source

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    Premisecitation

    Monogamous mandarin voles raised without a father socialize less and have fewer paraventricular oxytocin cells, a behavioral difference that can be reversed by optogenetic stimulation of paraventricular oxytocin terminals within the prelimbic cortex.

    “Monogamous mandarin voles raised without a father socialize less and have fewer PVN OXT cells, a behavioral difference that can be reversed by optogenetic stimulation of PVN OXT terminals within the prelimbic cortex (86).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] He, 2019, Increased anxiety and decreased sociability induced by paternal deprivation involve the PVN-PrL OTergic pathway, Elife. source

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    Premisecitation

    Paraventricular oxytocin cells in adults are active during interactions with juveniles, and stimulation of paraventricular oxytocin terminals in the ventral tegmental area increased social investigation through actions on OXTR.

    “PVN OXT cells in adults are also active during interactions with juveniles (85), and stimulation of PVN OXT terminals in the VTA increased social investigation through actions on OXTR specifically.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [85] Resendez, 2020, Social stimuli induce activation of oxytocin neurons within the paraventricular nucleus of the hypothalamus to promote social behavior in male mice, J Neurosci. source

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  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Oxytocin and vasopressin sources in the hypothalamus and extended amygdala play pivotal and distinct roles in social investigation, motivation, and social reward.

    “OXT and AVP sources in the hypothalamus and extended amygdala play pivotal and distinct roles in social investigation, motivation, and social reward (discussed later).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisenone given

    Bed nucleus of the stria terminalis vasopressin cell ablation and vasopressin knockdown both reduced male-male social investigation.

    “BNST AVP cell ablation and AVP knockdown both reduced male-male social investigation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin and vasopressin-expressing cells in the paraventricular and supraoptic nuclei send projections to the hippocampus, with the highest fiber density seen in the CA2 region for vasopressin and CA2/CA3 regions for oxytocin projections.

    “OXT and AVPexpressing cells in PVN and SON send projections to the hippocampus, with the highest fiber density seen in the CA2 region for AVP and CA2/CA3 regions for OXT projections (97-100).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [97] Zhang, 2013, Synaptic innervation to rat hippocampus by vasopressin-immuno-positive fibres from the hypothalamic supraoptic and paraventricular nuclei, Neuroscience. source

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    • cites [98] Cui, 2013, Hypothalamic and other connections with dorsal CA2 area of the mouse hippocampus, J Comp Neurol. source

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    • cites [99] Smith, 2016, Targeted activation of the hippocampal CA2 area strongly enhances social memory, Mol Psychiatry. source

      Not checked in the free run.

    • cites [100] Tirko, 2018, Oxytocin transforms firing mode of CA2 hippocampal neurons, Neuron. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Paraventricular oxytocin can facilitate social reward through its actions on brain dopamine systems originating in the ventral tegmental area and through endocannabinoid-dependent mechanisms.

    “PVN OXT can also facilitate social reward through its actions on brain dopamine systems (82), originating, for example, in the ventral tegmental area (VTA), and through endocannabinoid-dependent mechanisms (83).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [82] Hung, 2017, Gating of social reward by oxytocin in the ventral tegmental area, Science. source

      Not checked in the free run.

    • cites [83] Xiao, 2018, Oxytocin functions as a spatiotemporal filter for excitatory synaptic inputs to VTA dopamine neurons, Elife. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In California mice, knockdown of oxytocin or administration of an OXTR antagonist in the anterior bed nucleus of the stria terminalis increased social approach and decreased social vigilance, an anxiety-like behavior, suggesting that oxytocin may also drive social anxiety-like behavior depending on its source or context.

    “However, in California mice, knockdown of OXT or administration of OXTR antagonist in the anterior BNST increased social approach and decreased social vigilance, an anxiety-like behavior, which suggests that OXT may also drive social anxiety-like behavior depending on its source or context (66, 88).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [66] Duque-Wilckens, 2020, Extrahypothalamic oxytocin neurons drive stress-induced social vigilance and avoidance, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

    • cites [88] Duque-Wilckens, 2018, Oxytocin receptors in the anteromedial bed nucleus of the stria terminalis promote stress-induced social avoidance in female California mice, Biol Psychiatry. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In mice, bed nucleus of the stria terminalis and medial amygdala vasopressin cells are active during male sexual behavior and knockdown of vasopressin within the bed nucleus of the stria terminalis reduced the number of intromissions and ejaculations in males, but did not alter sexual behavior in females.

    “In mice, BNST and MeA AVP cells are active during male sexual behavior (101, 119) and knockdown of AVP within the BNST reduced the number of intromissions and ejaculations in males, but did not alter sexual behavior in females (91).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [101] Raam, 2017, Hippocampal oxytocin receptors are necessary for discrimination of social stimuli, Nat Commun. source

      Not checked in the free run.

    • cites [119] Ho, 2010, Vasopressin cell groups exhibit strongly divergent responses to copulation and male-male interactions in mice, Horm Behav. source

      Not checked in the free run.

    • cites [91] Rigney, 2021, Knockdown of sexually differentiated vasopressin expression in the bed nucleus of the stria terminalis reduces social and sexual behavior in male, but not female, mice, J Neuroendocrinol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pharmacological studies revealed that vasopressin in the anterior hypothalamus facilitates intermale aggression both in prairie voles and hamsters, while the opposite effect was found in female hamsters.

    “For example, pharmacological studies revealed that AVP in the anterior hypothalamus facilitates intermale aggression both in prairie voles and hamsters (16,43,116), while the opposite effect was found in female hamsters (117).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [16] Albers, 2015, Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network, Front Neuroendocrinol. source

      Not checked in the free run.

    • cites [43] Gobrogge, 2009, Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

    • cites [116] Ferris, 1997, Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters, J Neurosci. source

      Not checked in the free run.

    • cites [117] Gutzler, 2010, Arginine-vasopressin and the regulation of aggression in female Syrian hamsters (Mesocricetus auratus), Eur J Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin contributes to sexual arousal and sexual reward in males, while oxytocin influences lordosis and orgasm in females.

    “OXT contributes to sexual arousal and sexual reward in males, while OXT influences lordosis and orgasm in females (38).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Jurek, 2018, The oxytocin receptor: from intracellular signaling to behavior, Physiol Rev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In hamsters, social isolation increases aggression both in males and females, but V1aR density is higher in males than females.

    “In hamsters, social isolation increases aggression both in male and females, but V1aR density is higher in males than females (114).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [114] Terranova, 2017, Sex differences in the regulation of offensive aggression and dominance by arginine-vasopressin, Front Endocrinol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin is well known for its influence on social bonding and maternal behavior, and its role in parental behavior highlights the putative function of oxytocin as an attentional modulator.

    “OXT is well known for its influence on social bonding and maternal behavior (9,18), and its role in parental behavior highlights the putative function of OXT as an attentional modulator (122).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [9] Walum, 2018, The neural mechanisms and circuitry of the pair bond, Nat Rev Neurosci. source

      Not checked in the free run.

    • cites [18] Rilling, 2014, The biology of mammalian parenting and its effect on offspring social development, Science. source

      Not checked in the free run.

    • cites [122] Valtcheva, 2019, Neuromodulation of maternal circuits by oxytocin, Cell Tissue Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Bed nucleus of the stria terminalis vasopressin cell ablation impairs social recognition in males, likely through its projection to the lateral septum, and restoration of BNST-LS vasopressin signaling in Magel2-KO mice ameliorated social discrimination deficits.

    “For example, BNST AVP cell ablation impairs social recognition in males, likely through its projection to the LS (94, 108, 109), and restoration of BNST-LS AVP signaling in Magel2-KO mice ameliorated social discrimination deficits (110).”
    Quote in the paperSubstantial claim0 of 4 sources checked
    • cites [94] Bielsky, 2005, The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study, Neuron. source

      Not checked in the free run.

    • cites [108] Whylings, 2020, Sexually dimorphic role of BNST vasopressin cells in sickness and social behavior in male and female mice, Brain Behav Immun. source

      Not checked in the free run.

    • cites [109] Veenema, 2012, Vasopressin regulates social recognition in juvenile and adult rats of both sexes, but in sex- and age-specific ways, Horm Behav. source

      Not checked in the free run.

    • cites [110] Borie, 2021, Correction of vasopressin deficit in the lateral septum ameliorates social deficits of mouse autism model, J Clin Invest. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In rats, paraventricular oxytocin neurons are active during sexual behavior in males and females and blocking oxytocin action in the ventromedial hypothalamus and medial preoptic area reduces female receptivity.

    “In rats, PVN OXT neurons are active during sexual behavior in males and females and blocking OXT action in ventromedial hypothalamus and MPOA reduces female receptivity (38).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [38] Jurek, 2018, The oxytocin receptor: from intracellular signaling to behavior, Physiol Rev. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Constitutive knockout of Avpr1a in Syrian hamsters paradoxically increased flank marking and aggression in both sexes, highlighting the complex role of Avpr1a in territorial behaviors and potentially highlighting the role of compensatory mechanisms and/or effects on Avpr1a knockout in multiple brain regions.

    “Recently, constitutive KO of Avpr1a in Syrian hamsters paradoxically increased flank marking and aggression in both sexes, highlighting the complex role of Avpr1a in territorial behaviors and potentially highlighting the role of compensatory mechanisms and/or effects on Avpr1a KO in multiple brain regions (118).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [118] Taylor, 2022, CRISPR-Cas9 editing of the arginine-vasopressin V1a receptor produces paradoxical changes in social behavior in Syrian hamsters, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OXTRs in the anterior DG-CA2/CA3 circuit facilitate social, but not object discrimination, and vasopressin projections from the paraventricular nucleus to the hippocampus influence recognition of conspecifics as well as spatial features in mice.

    “OXTRs in the anterior DG-CA2/ CA3 circuit facilitate social, but not object discrimination (101), and AVP projections from PVN to hippocampus influence recognition of conspecifics as well as spatial features in mice (102).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [101] Raam, 2017, Hippocampal oxytocin receptors are necessary for discrimination of social stimuli, Nat Commun. source

      Not checked in the free run.

    • cites [102] Boyle, The geometry of hippocampal CA2 representations enables abstract coding of social familiarity and identity, bioRXiv.

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Vasopressin knockdown in the bed nucleus of the stria terminalis did not affect urine marking but did reduce other aspects of male communication (vocalizations and tail rattles), suggesting that BNST vasopressin is involved in some aspects of male offensive/territorial signaling.

    “However, AVP knockdown in this region did not affect urine marking but did reduce other aspects of male communication (eg, vocalizations and tail rattles), suggesting that BNST AVP is involved in some aspects of male offensive/territorial signaling (91).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [91] Rigney, 2021, Knockdown of sexually differentiated vasopressin expression in the bed nucleus of the stria terminalis reduces social and sexual behavior in male, but not female, mice, J Neuroendocrinol.

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Taken together, these studies suggest that vasopressin and oxytocin cells in the paraventricular nucleus help generate social preferences and influence social recognition by direct hippocampal, amygdala, and cortical synaptic release.

    “Taken together, these studies suggest that AVP and OXT cells in the PVN help generate social preferences and influence social recognition by direct hippocampal, amygdala, and cortical synaptic release.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    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.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [140] Borie, 2022, Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles, Curr Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Oxytocin and vasopressin are integrally involved in pair bonding in monogamous species, and mate choices more generally.

    “Thus, it is not surprising that OXT and AVP are integrally involved in pair bonding in monogamous species, and mate choices more generally.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Parental/sensory deprivation or cesarean delivery can lead to disruptions of hypothalamic oxytocin and maternal behavior, while in rats enriched environments increase hypothalamic oxytocin in dams and their male offspring.

    “Additionally, parental/sensory deprivation or cesarean delivery can lead to disruptions of hypothalamic OXT and maternal behavior (127-130), while, in rats, enriched environments increase hypothalamic OXT in dams and their male offspring (131).”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [127] Zheng, 2014, Oxytocin mediates early experience-dependent cross-modal plasticity in the sensory cortices, Nat Neurosci. source

      Not checked in the free run.

    • cites [128] Feng, 2019, Alteration in oxytocin levels induced by early social environment affects maternal behavior and estrogen receptor alpha in mandarin voles (Microtus mandarinus), Behav Brain Res. source

      Not checked in the free run.

    • cites [129] Li, 2021, Intranasal oxytocin restores maternal behavior and oxytocin neuronal activity in the supraoptic nucleus in rat dams with cesarean delivery, Neuroscience. source

      Not checked in the free run.

    • cites [130] Baracz, 2020, Maternal separation changes maternal care, anxiety-like behaviour and expression of paraventricular oxytocin and corticotrophin-releasing factor immunoreactivity in lactating rats, J Neuroendocrinol. source

      Not checked in the free run.

    • cites [131] Cutuli, 2019, Effects of pre-reproductive maternal enrichment on maternal care, offspring’s play behavior and oxytocinergic neurons, Neuropharmacology. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Variation in OXTR density in the nucleus accumbens is determined by genetic variation in the Oxtr gene, which in turn predicts how early-life nurturing experience affects later-life bonding ability.

    “This variation in OXTR density in the NAcc is determined by genetic variation in the Oxtr gene (144), which in turn predicts how early-life nurturing experience affects laterlife bonding ability (143).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [144] King, 2016, Variation in the oxytocin receptor gene predicts brain region-specific expression and social attachment, Biol Psychiatry. source

      Not checked in the free run.

    • cites [143] Ahern, 2021, Natural variation in the oxytocin receptor gene and rearing interact to influence reproductive and nonreproductive social behavior and receptor binding, Psychoneuroendocrinology. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxytocin from the paraventricular nucleus increases the salience of mouse pup vocalizations, while a dam's experience with pups adjusts the balance of excitatory and inhibitory tuning in the auditory cortex.

    “For example, OXT from PVN increases the salience of mouse pup vocalizations, while a dam's experience with pups adjusts the balance of excitatory and inhibitory tuning in the auditory cortex (54,123,124).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [54] Mitre, 2016, A distributed network for social cognition enriched for oxytocin receptors, J Neurosci. source

      Not checked in the free run.

    • cites [123] Marlin, 2015, Oxytocin enables maternal behaviour by balancing cortical inhibition, Nature. source

      Not checked in the free run.

    • cites [124] Schiavo, 2020, Innate and plastic mechanisms for maternal behaviour in auditory cortex, Nature. source

      Not checked in the free run.

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

    Interpretationreasoning

    While hypothalamic oxytocin plays a substantial role in rodent maternal behavior compared to vasopressin, the sources of vasopressin responsible for V1aR-mediated changes in parental behavior require further examination.

    “While hypothalamic OXT plays a substantial role in rodent maternal behavior compared to AVP, the sources of AVP responsible for V1aR-mediated changes in parental behavior require further examination.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Viral-mediated small interfering RNA knockdown of OXTR in the nucleus accumbens of prairie voles inhibits partner preference, while overexpressing NAcc OXTR enhances partner preference formation.

    “Viral-mediated small interfering RNA knockdown of OXTR in NAcc of prairie voles inhibits partner preference (138), while overexpressing NAcc OXTR enhances partner preference formation (139).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [138] Keebaugh, 2015, RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles, Soc Neurosci. source

      Not checked in the free run.

    • cites [139] Keebaugh, 2011, Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults, Horm Behav. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Although the precise sources of vasopressin regulating parental behavior are undefined, vasopressin projections from the extended amygdala may also influence maternal behavior, as vasopressin in the lateral septum facilitates paternal behavior in prairie voles.

    “Although the precise sources of AVP regulating parental behavior is undefined, AVP projections from the extended amygdala may also influence maternal behavior, as AVP in the LS facilitates paternal behavior in prairie voles (135, 136).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [135] Wang, 1994, Role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster), Proc Natl Acad Sci U S A. source

      Not checked in the free run.

    • cites [136] Bosch, 2008, Brain vasopressin is an important regulator of maternal behavior independent of dams’ trait anxiety, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Blocking brain oxytocin receptors in either sex prevents pair bonding, potentially disrupting coordinated activity across a social salience network.

    “Blocking brain OXT receptors in either sex prevents pair bonding, potentially disrupting coordinated activity across a social salience network (137).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [137] Johnson, 2016, Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles, Horm Behav. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The seminal paper demonstrating the effect of oxytocin on maternal behavior also showed that vasopressin stimulates maternal behavior, but with a longer latency of action.

    “However, the seminal paper demonstrating the effect of OXT on maternal behavior also showed that AVP stimulates maternal behavior, but with a longer latency of action (132).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [132] Pedersen, 1982, Oxytocin induces maternal behavior in virgin female rats, Science. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Paraventricular oxytocin neurons are activated when virgin mice observe pup retrievals by another mother and optogenetic stimulation of paraventricular oxytocin efferents to auditory cortex enhances pup retrieval learning in virgin mice.

    “Further, PVN OXT neurons are activated when virgin mice observe pup retrievals by another mother and optogenetic stimulation of PVN OXT efferents to auditory cortex enhances pup retrieval learning in virgin mice (124, 125).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [124] Schiavo, 2020, Innate and plastic mechanisms for maternal behaviour in auditory cortex, Nature. source

      Not checked in the free run.

    • cites [125] Carcea, 2021, Oxytocin neurons enable social transmission of maternal behaviour, Nature. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Robust individual differences in the nucleus accumbens relate to individual variation in alloparental nurturing behavior, and resilience to early-life adversity with respect to later-life pair bonding.

    “Robust individual differences in NAcc relate to individual variation in alloparental nurturing behavior, and resilience to early-life adversity with respect to later-life pair bonding (142, 143).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [142] Barrett, 2015, The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles, Transl Psychiatry. source

      Not checked in the free run.

    • cites [143] Ahern, 2021, Natural variation in the oxytocin receptor gene and rearing interact to influence reproductive and nonreproductive social behavior and receptor binding, Psychoneuroendocrinology. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    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).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [140] Borie, 2022, Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles, Curr Biol. source

      Not checked in the free run.

    • cites [141] Ross, 2009, Characterization of the oxytocin system regulating affiliative behavior in female prairie voles, Neuroscience. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Chemogenetic inhibition of paraventricular vasopressin cell activity increases nest building in male mice (while excitation decreases nest building in females), without altering other aspects of parental behavior.

    “Recent work has demonstrated that chemogenetic inhibition of PVN AVP cell activity increases nest building in male mice (while excitation decreases nest building in females), without altering other aspects of parental behavior (133).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [133] Bendesky, 2017, The genetic basis of parental care evolution in monogamous mice, Nature. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Prairie voles display empathy-based consoling behavior toward their distress partner, sibling, or familiar cage mate, which is mediated by OXTR in the anterior cingulate cortex, a region involved in empathetic responses in humans.

    “Prairie voles also display empathy-based consoling behavior toward their distress partner, sibling, or familiar cage mate, which is mediated by OXTR in the anterior cingulate cortex, a region involved in empathetic responses in humans (8).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Burkett, 2016, Oxytocin-dependent consolation behavior in rodents, Science. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    This experience-dependent change in OXTR signaling on physiology is mediated by OXTR-endocannabinoid interactions, and blocking CB1 receptor elicits defensive rejection by the female of the partner.

    “This experience-dependent change in OXTR signaling on physiology is mediated by OXTR-endocannabinoid interactions, and blocking CB1 receptor elicits defensive rejection by the female of the partner.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    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).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [140] Borie, 2022, Social experience alters oxytocinergic modulation in the nucleus accumbens of female prairie voles, Curr Biol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Oxtr knockout prairie voles display altered social preferences and reduced helping behavior toward a familiar cagemate.

    “Oxtr KO prairie voles display altered social preferences and reduced helping behavior toward a familiar cagemate (27,147).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [27] Horie, 2019, Oxytocin receptor knockout prairie voles generated by CRISPR/Cas9 editing show reduced preference for social novelty and exaggerated repetitive behaviors, Horm Behav. source

      Not checked in the free run.

    • cites [147] Kitano, 2022, Helping behavior in prairie voles: a model of empathy and the importance of oxytocin, iScience. source

      Not checked in the free run.

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

    Interpretationreasoning

    Consequently, it will be important to rebalance oxytocin/vasopressin research in behavioral neuroscience.

    “Consequently, it will be important to rebalance OXT/AVP research in behavioral neuroscience.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There is a disproportionate focus on oxytocin compared to vasopressin systems in research.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    More recent translational research suggests that both peptides have important clinical potential.

    “However, more recent translational research suggests that both peptides have important clinical potential.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Oxytocin has been more intensively investigated in this regard, and its therapeutic potential is related to its modulation of social motivation and the salience of social stimuli.

    “OXT has been more intensively investigated in this regard, and its therapeutic potential is related to its modulation of social motivation and the salience of social stimuli (19)(20)(21).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites (19)(20)(21)

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Viral-mediated Avpr1a receptor overexpression studies show that species differences in Avpr1a expression mediate species differences in social behavior, and variation in Avpr1a expression in the brain is related to microsatellite diversity in the gene's 5' flanking region.

    “Viral-mediated Avpr1a receptor overexpression studies show that species differences in Avpr1a expression mediate species differences in social behavior, and variation in Avpr1a expression in the brain is related to microsatellite diversity in the gene's 5′ flanking region (151-154).”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [151] Donaldson, 2013, The relative contribution of proximal 5′ flanking sequence and microsatellite variation on brain vasopressin 1a receptor (Avpr1a) gene expression and behavior, PLoS Genet. source

      Not checked in the free run.

    • cites [152] Lim, 2004, Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene, Nature. source

      Not checked in the free run.

    • cites [153] Hammock, 2005, Microsatellite instability generates diversity in brain and sociobehavioral traits, Science. source

      Not checked in the free run.

    • cites [154] Young, 1999, Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole, Nature. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Translational opportunities for oxytocin and vasopressin may extend beyond mental health as polymorphisms in V1aR and OXTR have been linked to variations in normal as well as disordered human behavior.

    “Translational opportunities for OXT and AVP may extend beyond mental health as polymorphisms in V1aR and OXTR have been linked to variations in normal as well as disordered human behavior (170).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [170] Aspé-Sánchez, 2015, Oxytocin and vasopressin receptor gene polymorphisms: role in social and psychiatric traits, Front Neurosci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Vasopressin stimulates partner preferences as well as selective aggression, or mate guarding, in male prairie voles.

    “AVP stimulates partner preferences as well as selective aggression, or mate guarding, in male prairie voles (15,148).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [15] Nair, 2006, Vasopressin and pair-bond formation: genes to brain to behavior, Physiology (Bethesda).

      Not checked in the free run.

    • cites [148] Donaldson, 2010, Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles, Behav Neurosci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    In zebrafish, oxytocin and OXTR drive social behavior in a context-dependent manner, suggesting a broad role of OXT/OXTR in social grouping.

    “In zebrafish, OXT and OXTR drive social behavior in a context-dependent manner, suggesting a broad role of OXT/ OXTR in social grouping (157, 158).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [157] Gemmer, 2022, Oxytocin receptors influence the development and maintenance of social behavior in zebrafish (Danio rerio), Sci Rep. source

      Not checked in the free run.

    • cites [158] Nunes, 2021, Developmental effects of oxytocin neurons on social affiliation and processing of social information, J Neurosci. source

      Not checked in the free run.

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

    Interpretationreasoning

    More attention needs to be devoted to understanding the contribution of different peptide sources and their specific targets, particularly with respect to vasopressin.

    “Specifically, more attention needs to be devoted to understanding the contribution of different peptide sources and their specific targets, particularly with respect to AVP (Fig. 2).”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There is a disproportionate focus on oxytocin compared to vasopressin systems in research.

  • May combine two claims.

    Interpretationcitation

    Thus, OXTR signaling promotes the adaptive mate preference of particular species, which in promiscuous species may be sexually dimorphic.

    “Thus, OXTR signaling promotes the adaptive mate preference of particular species, which in promiscuous species may be sexually dimorphic (28).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Yokoi, 2020, Sexually dimorphic role of oxytocin in medaka mate choice, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Single-cell transcriptomics studies show that paraventricular oxytocin neurons projecting within the brain that mediate social reward behaviors are disrupted in a mouse model of autism spectrum disorder, and those neurons are enriched for ASD-risk genes.

    “Single-cell transcriptomics studies show that PVN OXT neurons projecting within the brain that mediate social reward behaviors are disrupted in a mouse model of ASD, and those neurons are enriched for ASD-risk genes (159).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [159] Lewis, 2020, Parallel social information processing circuits are differentially impacted in autism, Neuron. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    V1aR signaling in the ventral pallidum and lateral septum promote partner preferences, while pair bond-induced aggression is mediated by V1aR in the lateral hypothalamus.

    “V1aR signaling in the ventral pallidum and LS promote partner preferences (149), while pair bond-induced aggression is mediated by V1aR in the lateral hypothalamus (43,150).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites [149] Young, 2004, The neurobiology of pair bonding, Nat Neurosci. source

      Not checked in the free run.

    • cites [43] Gobrogge, 2009, Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

    • cites [150] Barrett, 2013, Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles, Horm Behav. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Modern molecular approaches are greatly enhancing our understanding of how and where oxytocin and vasopressin act to regulate social processes.

    “Modern molecular approaches are greatly enhancing our understanding of how and where OXT and AVP act to regulate social processes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Voles display remarkable individual variation in V1aR density in the retrosplenial cortex, a region involved in spatial memory, and this receptor density is related to Avpr1a polymorphisms, space use in relation to nesting, and sexual fidelity in males.

    “Voles display remarkable individual variation in V1aR density in the retrosplenial cortex (155), a region involved in spatial memory, and this receptor density is related to Avpr1a polymorphisms, space use in relation to nesting, and sexual fidelity in males (156).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [155] Phelps, 2003, Extraordinary diversity in vasopressin (V1a) receptor distributions among wild prairie voles (Microtus ochrogaster): patterns of variation and covariation, J Comp Neurol. source

      Not checked in the free run.

    • cites [156] Okhovat, 2015, Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain, Science. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S4 (based).

    Premisenone given

    Considerably more attention has been directed toward the oxytocin system than the vasopressin system in the past decade because of its perceived translational applications.

    “Despite this progress, considerably more attention has been directed toward the OXT system than the AVP system in the past decade because of its perceived translational applications.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: There is a disproportionate focus on oxytocin compared to vasopressin systems in research.

  • May combine two claims.

    Interpretationcitation

    Clinically, the efficacy of intranasally delivered oxytocin has been mixed, and there is a critical need for clinical trials to be designed based on our understanding of oxytocin's function in the brain, such as enhancing the salience of social stimuli.

    “Clinically, the efficacy of intranasally delivered OXT has been mixed, and there is a critical need for clinical trials to be designed based on our understanding of OXT's function in the brain, such as enhancing the salience of social stimuli (20).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Ford, 2022, Refining oxytocin therapy for autism: context is key, Nat Rev Neurol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Females with targeted Oxt or Oxtr mutations lose preference for familiar males and mate indiscriminately, while Oxt or Oxtr mutant males preferentially mate with familiar females.

    “Females with targeted Oxt or Oxtr mutations lose preference for familiar males and mate indiscriminately, while Oxt or Oxtr mutant males preferentially mate with familiar females.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [28] Yokoi, 2020, Sexually dimorphic role of oxytocin in medaka mate choice, Proc Natl Acad Sci U S A. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Thus, both oxytocin and vasopressin mediate adaptive sociosexual behaviors across vertebrate taxa, although the behavior that is adaptive may differ across species.

    “Thus, both OXT and AVP mediate adaptive sociosexual behaviors across vertebrate taxa, although the behavior that is adaptive may differ across species.”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    The incorporation of modern molecular genetic approaches into studies of alternative model organisms with diverse social systems is essential for gaining a complete understanding of oxytocin and vasopressin function in the brain, and thereby maximizing translational opportunities.

    “Finally, the incorporation of modern molecular genetic approaches into studies of alternative model organisms with diverse social systems is essential for gaining a complete understanding of OXT and AVP function in the brain, and thereby maximizing translational opportunities (19,174).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [19] Ford, 2021, Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry, Curr Opin Neurobiol. source

      Not checked in the free run.

    • cites [174] Johnson, 2018, Evolutionary diversity as a catalyst for biological discovery, Integr Zool. source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    Medaka fish are promiscuous breeders of which females prefer to mate with familiar males that manage to maintain proximity to the female despite efforts of competing males, while males mate indiscriminately.

    “Medaka fish are promiscuous breeders of which females prefer to mate with familiar males that manage to maintain proximity to the female despite efforts of competing males, while males mate indiscriminately.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In another autism spectrum disorder mouse model, OXTR signaling in ventral tegmental area dopamine neurons, which mediate social reward, is disrupted, and a kinase inhibitor that restores OXTR signaling also restores disrupted ASD-relevant social behaviors.

    “In another ASD mouse model, OXTR signaling in VTA dopamine neurons, which mediate social reward, is disrupted, and a kinase inhibitor that restores OXTR signaling also restores disrupted ASD-relevant social behaviors (161).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Hörnberg, 2020, Rescue of oxytocin response and social behaviour in a mouse model of autism, Nature. source

      Not checked in the free run.

82 of 82

  • The paper relies on this without support.

    There is a disproportionate focus on oxytocin compared to vasopressin systems in research.

    “Importantly, the disproportionate focus on OXT compared to AVP systems suggests there is a need to rebalance research so that the role of different AVP circuits in social behavior can be refined and expanded.”
    “Despite this progress, considerably more attention has been directed toward the OXT system than the AVP system in the past decade because of its perceived translational applications.”
1 of 1

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?

  • Oxytocin promotes prosocial behavior, bonding, and the saliency of social cues in humans and other mammals.

    “Research in humans and in other mammals demonstrates a role for OT in promoting prosocial behavior, bonding, and the saliency of social cues [9,23,24].”

    From The Neurobiology of Love and Pair Bonding from Human and Animal Perspectives (2023) · cites this paper as [23]

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Ferris, 1984, Vasopressin injected into the hypothalamus triggers a stereotypic behavior in golden hamsters, Science., 224, 521, 10.1126/science.6538700 · DOI · Paper page

Cited by

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Related

Authors
Rigney, N., de Vries, G. J., Petrulis, A., & Young, L. J.
Affiliations
  • Georgia State University (US)
  • Neuroscience Institute and Center for Behavioral Neuroscience, Georgia State University , Atlanta, Georgia 30303 , USA
  • Emory University (US)
Corresponding author
Young, Larry J
ORCID
Venue
Endocrinology
Publisher
The Endocrine Society
Published
2022-07-21
Volume
163
Issue
9
ISSN
  • 0013-7227 (ISSN-L)
  • 1945-7170
DOI
10.1210/endocr/bqac111
PMC
PMC9337272
OpenAlex
W4286499612
Semantic Scholar
bc0e5af87b23a1d498327fc9bd4d5dca0b629e49
Cited by
191
References
173
Citations by year
2026: 54 · 2025: 61 · 2024: 44 · 2023: 28 · 2022: 4
FWCI
5.13
Type
journal article
Language
en
Open access
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)
Locations
  • Endocrinology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (R01MH115831, P50MH100023, R01MH112788, R01 MH121603, R03 MH120549, F31 MH125659)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
oxytocin, vasopressin, social behavior, neural circuits, neuropeptide systems, social memory, pair bonding, monogamy, social communication, aggression, territoriality, social reward, autism spectrum disorder, social dysfunction, species differences, translational research
MeSH terms
Autism Spectrum Disorder, Animals, Humans, Male, Oxytocin, Pair Bond, Social Behavior, Vasopressins, Receptors, Oxytocin

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.

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