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Cited by 66Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyPrimate Behavior and Ecology

Neuropeptide diversity and the regulation of social behavior in New World primates

Open access
French, Jeffrey A., Taylor, Jack H., Mustoe, Aaryn C., Cavanaugh, Jon·2016·Frontiers in Neuroendocrinology
DOI 10.1016/j.yfrne.2016.03.004PMC PMC5030117
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Abstract

Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology, and have emerged as important modulators of brain function, particularly in the social realm. OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals, but recent discoveries have identified surprising variability in OT and peptide structure in New World monkeys (NWM), with five new OT variants identified to date. This review explores these new findings in light of comparative OT/AVP ligand evolution, documents coevolutionary changes in the oxytocin and vasopressin receptors (OTR and V1aR), and highlights the distribution of neuropeptidergic neurons and receptors in the primate brain. Finally, the behavioral consequences of OT and AVP in regulating NWM sociality are summarized, demonstrating important neuromodulatory effects of these compounds and OT ligand-specific influences in certain social domains.

AI snapshot

Written from the paper’s full text.

TL;DR

This review argues that the textbook view of strict oxytocin conservation in eutherian mammals is untenable: New World monkeys express six OT ligand variants while AVP remains conserved, with coevolutionary changes in OTR/V1aR and links to social monogamy and behavior. It synthesizes genomic, receptor, neuroanatomical, and behavioral evidence to position NWM as a natural experiment for nonapeptide modulation of sociality.

Key findings

  • NWM have six OT ligand variants total: consensus Leu8-OT plus five novel variants (Pro8-, Thr8-, Ala8-, Phe2-, and Val3-Pro8-OT), whereas AVP is identical to consensus mammalian AVP across all primates studied; eutherian OXT dN/dS is 0.009 and AVP dN/dS is 0.005.
  • OTR and V1aR show coevolution with ligand and social structure: OTR phylogeny groups by OT variant, social monogamy, and paternal care; Ateles OTR resembles Cebidae despite canonical phylogeny; V1aR substitutions including Gly172, Cys241, Asn319, and Val399 are associated with social monogamy, and social monogamy occurs in more than 62% of the 117 NWM species.
  • Behavioral studies show ligand- and context-specific effects: IN Pro8-OT in marmosets reduced proximity/sociosexual behavior toward opposite-sex strangers and increased latency to sociosexual behavior, while Leu8-OT did not; high-dose IN AVP in male titi monkeys increased affiliation with their pairmate over strangers; an OT antagonist increased male cortisol and reduced proximity to the mate during a stressor.
  • Neuroanatomically, OTR and V1aR are widely distributed in the social decision-making network but differ across primates: Callithrix has dense OTR in NAcc, Callicebus instead densely expresses V1aR there, and OTR is present in visual sensory centers such as SC and NBM across Callithrix, Callicebus, Macaca, and Homo.

Methods

  • Narrative review and synthesis; no new primary experimental data are reported. It integrates comparative genomics of OXT/AVP and OXTR/AVPR1A, phylogenetic analyses, receptor alignments, neuroanatomical mapping, and behavioral pharmacology in NWM.
  • Data are drawn from published studies across primates and other vertebrates, including a receptor coevolution survey of 69 invertebrate and vertebrate species, multiple NWM genera (Callithrix, Callicebus, Saimiri, and others), and behavioral studies mostly in marmosets, tamarins, and titi monkeys.
  • Main analyses summarized include dN/dS ratios, phylogenetic trees, amino acid substitution mapping, and review of agonist/antagonist and intranasal neuropeptide experiments.

Limitations

  • Stated: large gaps remain in the primate neuroanatomical map of OT/AVP neurons, projections, and receptors; primate radioligand autoradiography has selectivity and cross-reactivity limitations; binding affinities for NWM OT variants and ligand-receptor crosstalk data are needed.
  • Stated: intranasal OT studies face caveats including supraphysiological doses, only about 0.005% of administered neuropeptide accumulating in CSF within an hour, possible peripheral pathway effects, and peripheral OT measures not directly reflecting central release.
  • Evident: the review relies on limited species and studies, many behavioral conclusions come from marmosets, primate sex-difference data are sparse, and some neuroanatomical studies used Leu8-OT reagents before Pro8-OT was discovered in marmosets.

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

Integrity signals

Registry

Crossref · 10.1016/j.yfrne.2016.03.004

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 237 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    The dN/dS ratio for the ligand-coding region of AVP is remarkably low (0.005), suggesting extreme conservation of AVP ligand structure across eutherian mammals.

    “dN/dS ratios for the ligand-coding region of AVP are also remarkably low (0.005), again suggesting extreme conservation of AVP ligand structure across eutherian mammals.”
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    • cites Wallis, 2012 source

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  • Premisecitation

    The incidence of social monogamy among New World monkeys is exceptionally high: more than 62 percent of the 117 species in this primate group are classified as socially monogamous.

    “the incidence of social monogamy among NWM, in various forms, is exceptionally high – more than 62% of the 117 species in this primate group are classified as socially monogamous (Lukas and Clutton-Brock, 2013)”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Lukas and Clutton-Brock, 2013

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  • Premisenone given

    AVP structure is conserved within New World monkeys.

    “while AVP structure is conserved within this group of primates (as it is in most eutherian mammals)”
    Quote in the paperNot a substantial claim
  • Premisecitation

    OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals.

    “OT structure and the genes that ultimately determine structure are highly conserved among diverse eutherian mammals”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Wallis, 2012 source

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  • Premisecitation

    The dN/dS ratio for eutherian OXT is strikingly low: 0.009.

    “dN/dS for eutherian OXT is strikingly low: 0.009.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wallis, 2012 source

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  • Classified as probably not a substantial claim. 43
  • May combine two claims. 94

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

    Premisenone given

    Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology and modulate brain function, particularly in the social realm.

    “Oxytocin (OT) and vasopressin (AVP) are important hypothalamic neuropeptides that regulate peripheral physiology, and have emerged as important modulators of brain function, particularly in the social realm.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    OT is critical in the formation and maintenance of mother-infant bonds in mammals.

    “OT has been shown to be critical in the formation and maintenance of mother-infant bonds in mammals (Rilling and Young, 2014)”
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    • cites Rilling and Young, 2014 source

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    Premisecitation

    Social monogamy is a rare mating system among mammals, estimated at between 3 and 9 percent of mammalian species.

    “social monogamy is a rare mating system among mammals (estimated between 3 – 9% of mammalian species; (Kleiman, 1977; Lukas and Clutton-Brock, 2013)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Kleiman, 1977 source

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    • cites Lukas and Clutton-Brock, 2013

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  • May combine two claims.

    Premisenone given

    OT structure is highly variable in New World monkeys, with six variants identified to date.

    “OT structure is highly variable in this group, with six variants identified to date”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OT and AVP regulate social behavior beyond the maternal context, including social attachments among adults, social cognition, and aggression.

    “There is also a growing interest in OT and the related neurohypophyseal nonapetide arginine vasopressin (AVP) and their analogues in the regulation of social behavior beyond the maternal context, including social attachments among adults, social cognition, and aggression”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Albers, 2015 source

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    • cites Caldwell and Young III, 2006

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    • cites Donaldson and Young, 2008 source

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    Premisecitation

    Primates as an Order diverged from other mammalian forms approximately 80-90 million years ago.

    “Primates as an Order diverged from other mammalian forms approximately 80-90 million years ago (Mya; (Perelman et al., 2011)”
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    • cites Perelman et al., 2011 source

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    Interpretationreasoning

    The one mammalian taxon in which social monogamy is the norm among species also represents the only mammalian taxon where there are multiple documented mutations in the OXT gene.

    “the one mammalian taxon in which social monogamy is the norm among species also represents the only mammalian taxon where there multiple documented mutations in the OXT gene”
    Quote in the paperNot a substantial claim

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    Premisecitation

    In nonmammalian vertebrates and the opossum, the genes for the two nonapeptides are arranged tail-to-head, whereas in eutherian mammals the AVP and OT genes are arranged tail-to-tail.

    “In nonmammalian vertebrates and the opossum, genes for the two nonapeptides are arranged tail-to-head, indicating that transcription occurs from the same DNA strand. In contrast, AVP and OT genes are arranged tail-to-tail in all eutherian mammals”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Gwee et al., 2009, 2008

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

    • cites Wallis, 2012 source

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    • cites Yamashita and Kitano, 2013 source

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

    Premisenone given

    Most vertebrates express two forms of the nonapeptide: an OT-like and an AVP-like ligand.

    “Most vertebrates express two forms: an OT- and an AVP-like ligand.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    New World monkeys comprise the parvorder Platyrrhini, and divergence of this taxon from Old World primates and hominoids occurred approximately 43 million years ago.

    “NWM comprise the parvorder Platyrrhini, and estimates based on molecular clocks suggest a divergence of this taxon from Old World primates and hominoids ~43 Mya”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Perelman et al., 2011 source

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    • cites Schneider and Sampaio, 2015

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    • cites Wildman et al., 2009 source

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

    Premisecitation

    The OT lineage is presumed to have evolutionary origins in reproductive function, while the AVP lineage is presumed to have origins in the regulation of fluid homeostasis.

    “The OT lineage (isotocin-mesotocin-oxytocin) is presumed to have evolutionary origins in the service of reproductive function, while the AVP lineage (vasotocin-vasopressin) is presumed to have origins in the regulation of fluid homeostasis”
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    • cites Acher, 1996 source

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    Premisenone given

    Within New World monkeys there are 17 genera classified into three families: Pithecidae, Atelidae, and Cebidae.

    “Within this taxon there are 17 genera that are classified into three families: Pithecidae (Callicebus, Cacajao, Pithecia, and Chiropotes), Atelidae (Ateles, Brachyteles, Lagothrix, and Alouatta), and Cebidae (Saimiri, Cebus, Aotus, Saguinus, Leontopithecus, Callimico, Cebuella, Mico, and Callithrix).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    New World primates represent the first eutherian mammalian taxon in which OT structural variants were documented, and these variants appeared in some, but not all, New World monkeys.

    “Thus, New World primates represent the first eutherian mammalian taxon in which OT structural variants were documented, and these variants appeared in some, but not all, NWM.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Pithecidae diverged from Atelidae/Cebidae approximately 25 million years ago, and the divergence between Atelidae and Cebidae occurred approximately 23 million years ago.

    “Pithecidae diverged from Atelidae/Cebidae ~25 Mya, and the divergence between Atelidae and Cebidae occurred ~23 Mya.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Pitheciidae and Atelidae are generally large-bodied frugivore/folivore species, while Cebidae are small-bodied species with more varied diets.

    “Pitheciidae and Atelidae are generally large-bodied frugivore/folivore species (1.0 – 3.0 kg and 7.0 – 9.0 kg, respectively), while Cebidae are small-bodied species with more varied diets (0.12 – 2.5 kg; Smith and Jungers, 1997).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Smith and Jungers, 1997

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    Premisecitation

    Each of the amino acid substitutions in positions 2, 3, and 8 in New World monkey OT ligands represents at least one physicochemical change from the corresponding residue in consensus mammalian OT, and hence these changes can be classified as 'radical' amino acid substitutions.

    “Each of the amino acid substitutions in positions 2, 3, and 8 in NWM represents at least one physicochemical change (polarity, charge, or hydrophobicity) from the corresponding residue in consensus mammalian OT. Hence these changes can be classified as ‘radical’ amino acid substitutions (Zhang, 2000)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zhang, 2000 source

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    Premisecitation

    Phe2-OT is the most hydrophobic variant, Leu8-OT is intermediate, while Pro8-OT is the most hydrophilic of the OT variants.

    “For instance, Phe2-OT is the most hydrophobic variant, Leu8-OT is intermediate, while Pro8-OT is the most hydrophilic of the variants (Ren et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ren et al., 2015 source

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  • May combine two claims.

    Premisenone given

    While Pro8-OT is the most hydrophilic of the OT variants, it is still more hydrophobic than AVP.

    “While the Pro8-OT variant is the most hydrophilic of the OT variants, it is still more hydrophobic than AVP.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    Within Pitheciidae, Callicebus maintains Leu8-OT, and two mutations at least ~14 million years ago led to Thr and Ala substitutions at position 8 in Pithecia and Chiropotes/Cacajao, respectively.

    “Within the Pitheciidae, Callicebus maintains Leu8-OT, and two mutations at least ~14 Mya led to Thr and Ala substitutions at position 8 in Pithecia and Chiropotes/Cacajao, respectively.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    The tandem Pro-Pro sequence in positions 7 and 8 produces a polyproline helix, a feature that can significantly alter ligand-cell membrane interaction profiles.

    “Further, the tandem Pro-Pro sequence in positions 7 and 8 produces a polyproline helix, a feature that can significantly alter ligand-cell membrane interaction profiles (Geisler and Chmielewski, 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Geisler and Chmielewski, 2009

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  • May combine two claims.

    Premisereasoning

    Within Atelids, at least two independent mutations likely occurred, one at ~16 million years ago leading to Phe2-OT in Alouatta, and one at ~11 million years ago leading to Pro8-OT in Ateles.

    “Within the Atelids, at least two independent mutations likely occurred, one at ~16 Mya leading to Phe2-OT in Alouatta, and one at ~11 Mya leading to Pro8-OT in Ateles.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Given the presence of multiple OT variants within New World monkey families, mutations in the mature peptide coding regions of OXT continued after separation of the three distinct clades, and some mutations have occurred in recent evolutionary time.

    “Given the presence of multiple OT variants within NWM families, it is clear that mutations in the mature peptide coding regions of OXT continued after separation of the three distinct clades, and some mutations have occurred in recent evolutionary time.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    None of the genera in the family Cebidae express Leu8-OT, but all genera have a nonsynonymous substitution in the 8th codon (CTG to CCG) leading to a proline residue in the 8th position.

    “None of the genera in the family Cebidae express Leu8-OT, but all genera have a NS in the 8th codon (CTG → CCG) leading to a proline residue in the 8th position.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ren et al., 2015 source

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  • May combine two claims.

    Premisereasoning

    The branching of Cebidae from the other New World monkey families ~23 million years ago was likely associated with a mutation that led to the second instance of Pro8-OT in New World monkeys, and a recent nucleotide substitution led to a Val substitution at position 3 in three species of Saguinus.

    “The branching of Cebidae from the other NWM families ~23 Mya was likely associated with a mutation that led to the second instance of Pro8-OT in NWM, and a recent nucleotide substitution has led to a Val substitution at position 3 in three species of bare-faced tamarins (Saguinus), in addition to the Cebidae-specific Pro substitution at position 8.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    OTRs are distributed widely in target tissues throughout the periphery and in the brain.

    “OTRs are distributed widely in target tissues throughout the periphery and in the brain (see Section 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    The Pro8 substitution in two OT variants produces a dramatic alteration in the structure of the 'tail' portion of the OT molecule, whereas the other residue substitutions produce only minor, but still potentially significant, alterations in chemical structure.

    “Figure 2 portrays two-dimensional structural models of the six NWM OT variants, and it is clear that the Pro8 substitution in two OT variants produces a dramatic alteration in the structure of the ‘tail’ portion of the OT molecule, whereas the other residue substitutions produce only minor, but still potentially significant, alterations in chemical structure.”
    Quote in the paperSubstantial claim

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

    Premisenone given

    Neuropeptide signaling requires four elements: synthesis of the peptide modulator by cells of origin, transport of the peptide to target cells, recognition and binding of the peptide by appropriate cellular receptors, and modification of cell function via intracellular signaling cascades.

    “Neuropeptide signaling requires four elements: (1) the synthesis of the peptide modulator by cells of origin, (2) the transport of the peptide to target cells, (3) recognition and binding of the peptide by appropriate cellular receptors, and (4) modification of cell function via intracellular signaling cascades.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    The change from Leu8-OT to Pro8-OT has been identified as a more dramatic change in the molecular architecture of OT than the change from mesotocin to consensus mammalian OT, with the potential for significant functional changes in the mechanisms of OT binding and signaling.

    “The change from Leu8-OT to Pro8-OT has been identified as a more dramatic change in the molecular architecture of OT than the change from mesotocin to consensus mammalian OT (in which Isoleucine in replaced by Leucine at position 8; Stoop, 2012), with the potential for significant functional changes in the mechanisms of OT binding and signaling.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Stoop, 2012 source

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

    Premisenone given

    Four receptor types have been identified in mammals: a single receptor that binds OT (OTR), and three receptor subtypes that bind AVP (V1aR, V1bR, and V2R).

    “Four receptor types have been identified in mammals: a single receptor that binds OT (OTR), and three receptor subtypes that bind AVP (V1aR, V1bR, and V2R).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A recent search on OT coding nucleotides among eutherian mammals suggests at least two additional variants: Leu3-OT in armadillo, and Thr4-Val8-OT in big brown bats.

    “a recent search on OT coding nucleotides among eutherian mammals suggests at least two additional variants: Leu3-OT in armadillo, and Thr4-Val8-OT in big brown bats (data accessed from NCBI; 12/15/2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites NCBI

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

    Premisereasoning

    In OT and AVP signaling, recognition/binding and modification of cell function are accomplished by cell membrane bound G protein-coupled receptors (GPCRs).

    “In the case of OT and AVP signaling, the latter two functions are accomplished by cell membrane bound G protein-coupled receptors (GPCRs).”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    These receptors are members of the Class I (or A) rhodopsin-like GPCR family.

    “These receptors are members of the Class I (or A) rhodopsin-like GPCR family.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisereasoning

    There are at least two evolutionary 'hot-spots' where diversity in OT ligand structure is apparent in limited taxonomic groups: sharks, skates, and rays (five OT-like ligand variants) and New World monkeys (six OT ligand variants).

    “there are at least two evolutionary ‘hot-spots’ where diversity in OT ligand structure is apparent in limited taxonomic groups: sharks, skates, and rays (five OT-like ligand variants) and NWM (six OT ligand variants).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    V2R is primarily expressed in the kidney, and mediates the antidiuretic effects of AVP.

    “V2R is primarily expressed in the kidney, and mediates the antidiuretic effects of AVP (Bankir, 2001)”
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    • cites Bankir, 2001 source

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

    Premisecitation

    OTR and V1aR are classic neuromodulators, mediating both short- and long-term changes in neural and hence behavioral outcomes.

    “OTR and V1aR are classic neuromodulators, mediating both short- and long-term changes in neural and hence behavioral outcomes (Owen et al., 2013).”
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    • cites Owen et al., 2013 source

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

    Premisecitation

    AVP binding involves interactions with amino acid residues in all three extracellular loop elements and residues in the N-terminus proximal to the first TM segment.

    “AVP binding, in contrast, involves interactions with amino acid residues in all three extracellular loop elements and residues in the N-terminus proximal to the first TM segment. (Hawtin et al., 2005; Thibonnier et al., 2000).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hawtin et al., 2005 source

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    • cites Thibonnier et al., 2000 source

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

    Premisecitation

    The ring portion of OT interacts with the first extracellular loop of OTR, while the 3-residue tail structure interacts with the extracellular N-terminal domain.

    “The ring portion of OT interacts with the first extracellular loop of OTR, while the 3-residue tail structure interacts with the extracellular N-terminal domain (Gimpl and Fahrenholz, 2001; Zingg and Laporte, 2003).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gimpl and Fahrenholz, 2001 source

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    • cites Zingg and Laporte, 2003

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

    Premisecitation

    Growing evidence suggests an important role for V1bR in behavioral and neuroendocrine modulation.

    “Growing evidence suggests an important role for V1bR in behavioral and neuroendocrine modulation (Griebel et al., 2003; Smith et al., 2016; Stevenson and Caldwell, 2012).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Griebel et al., 2003 source

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    • cites Smith et al., 2016 source

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    • cites Stevenson and Caldwell, 2012

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

    Premisenone given

    V1aR and V1bR are expressed widely in peripheral tissue, but are also expressed throughout the central nervous system.

    “V1aR and V1bR are likewise expressed widely in peripheral tissue, but are also expressed throughout the central nervous system.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    In both OT and AVP signaling, multiple changes in cell function arise from G protein activation, including mobilization of Ca2+ ions from intracellular stores, alteration of voltage and ligand gated ion channels, and induction of enzymes for neurotransmitter biosynthesis.

    “In both cases, multiple changes in cell function arise from G protein activation, including mobilization of Ca2+ ions from intracellular stores, alteration of voltage and ligand gated ion channels, and induction of enzymes for neurotransmitter biosynthesis (Stoop, 2014, 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Stoop, 2014, 2012

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premisenone given

    There are conserved elements of the peptide ligands (positions 1, 6, and 9) but also considerable variability in other positions (2-5 and 8).

    “There are conserved elements of the peptide ligands (positions 1, 6, and 9) but also considerable variability in other positions (2-5 and 8; see Table 1).”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    This analysis focuses on interspecific differences in OTR and V1aR structure in three New World monkey model species: Callithrix (Pro8-OT; socially monogamous), Callicebus (Leu8-OT; socially monogamous), and Saimiri (Pro8-OT; nonmonogamous).

    “This analysis focuses on interspecific differences in OTR and V1aR structure in three important NWM model species that vary in both OT ligand and in social structure: Callithrix: (Pro8-OT; socially monogamous), Callicebus (Leu8-OT; socially monogamous), and the Saimiri (Pro8-OT; nonmonogamous).”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Studying the OT/AVP nonapeptide family and the corresponding structure of their cognate receptors serves as an interesting test case in ligand-receptor coevolution, given the long evolutionary history of these peptide systems (~600 million years) and evolutionary changes in ligand structure.

    “Studying the OT/AVP nonapeptide family and the corresponding structure of their cognate receptors serves as an interesting test case in ligand-receptor coevolution (Markov et al., 2008), given the long evolutionary history of these peptide systems (~600 million years) and evolutionary changes in ligand structure.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Markov et al., 2008 source

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  • May combine two claims.

    Interpretationreasoning

    The variable amino acids at positions 2-5 and 8 are likely responsible for species-specific recognition at the receptor level and may underlie the multitude of functions subserved by nonapeptides.

    “The variable amino acids at positions 2-5 and 8 are likely responsible for species-specific recognition at the receptor level and may underlie the multitude of functions subserved by nonapeptides.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    AVP ligand binding to V1aR activates two potential signaling cascades via Gq and Gi/o proteins, which can open nonspecific cationic channels or close K+ channels.

    “AVP ligand binding to V1aR activates two potential signaling cascades via Gq and Gi/o proteins, which can open nonspecific cationic channels or close K+ channels (reviewed in Caldwell et al., 2008; Gimpl and Fahrenholz, 2001).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Caldwell et al., 2008 source

      Not checked in the free run.

    • cites Gimpl and Fahrenholz, 2001 source

      Not checked in the free run.

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

    Premisecitation

    OT ligand binding to OTR activates multiple G proteins that can exert diverse effects on cell function, including stimulation of cAMP (Gs), inhibition of adenylyl cyclase (Gi/o), stimulation of potassium channel currents (Gi) and activation of phospholipase C (Gq).

    “OT ligand binding to OTR activates multiple G proteins that can exert diverse effects on cell function, including stimulation of cAMP (Gs), inhibition of adenylyl cyclase (Gi/o), stimulation of potassium channel currents (Gi) and activation of phospholipase C (Gq).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Caldwell et al., 2008 source

      Not checked in the free run.

    • cites Gimpl and Fahrenholz, 2001 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Nonapeptide receptor nucleotide sequences differentiate primate taxa, with significant bootstrap support in most cases.

    “When a similar phylogenetic analysis is conducted on nonapeptide receptor variability among primates, taxa can be differentiated on the basis of receptor nucleotide sequences (Fig. 4a), in most cases with significant bootstrap support (Ren et al., 2014, 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ren et al., 2014, 2015

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • May combine two claims.

    Premiseown data

    Receptors for invertebrate species that only possess vasopressin-like ligands clearly cluster together and are distinct from all nonapeptide receptors for vertebrates.

    “First, receptors for invertebrate species that only possess vasopressin-like ligands clearly cluster together and are distinct from all nonapeptide receptors for vertebrates.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Humans and Callithrix are more closely related to each other than to Otolemur, but Otolemur and human share the Leu8-OT.

    “Humans and Callitrix are more closely related to each other than to Otolemur, but Otolemur and human share the Leu8-OT.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Ren et al., 2015 source

      Not checked in the free run.

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

    Interpretationnone given

    Differences in OTR structure based solely on evolutionary distance would result in more amino acid differences between Homo and Otolemur than between Homo and Callithrix.

    “Differences in OTR structure based solely on evolutionary distance would result in more amino acid differences between Homo and Otolemur than between Homo and Callithrix.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Receptor structure for different species expressing the three classic OT-like ligand variants (isotocin, mesotocin, and oxytocin) show high receptor sequence similarity among common ligands, but are clearly differentiated across OT-like ligands.

    “Third, and perhaps most importantly, receptor structure for different species expressing the three classic OT-like ligand variants (isotocin, mesotocin, and oxytocin) show high receptor sequence similarity among common ligands, but are clearly differentiated across OT-like ligands.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premiseown data

    Ateles is the only genus of New World monkey outside Cebidae to express Pro8-OT, and all Cebids express this OT variant.

    “As shown in Section 3.2, Ateles is the only genera of NWM outside the Cebidae to express Pro8-OT, and all Cebids express this OT variant.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Within New World monkeys, OTR sequence phylogenies significantly group by OT variants, social monogamy, and paternal care.

    “examining OTR sequence phylogeny within the NWMs demonstrates OTR sequence phylogenies also significantly group by OT variants, social monogamy (Ren et al., 2015), and paternal care (Vargas-Pinilla et al., 2015).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Ren et al., 2015 source

      Not checked in the free run.

    • cites Vargas-Pinilla et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    OTR variability among primates and especially New World monkeys has been significantly associated with social monogamy and paternal care in New World monkeys.

    “OTR variability among primates and especially NWM has been significantly associated with the occurrence of two important social phenotypes in NWM: social monogamy (Ren et al., 2015) and paternal care in (Vargas-Pinilla et al., 2015).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Ren et al., 2015 source

      Not checked in the free run.

    • cites Vargas-Pinilla et al., 2015 source

      Not checked in the free run.

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

    Interpretationcitation

    Structural changes to the C-terminus tail of the Pro8-OT ligand might result in compensatory amino acid substitutions in the N-terminus of the receptor.

    “It is reasonable that structural changes to the C-terminus tail of the Pro8-OT ligand might result in compensatory amino acid substitutions in the N-terminus of the receptor (Ren et al., 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Ren et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The F103Y residue is homologous to Tyr115 in V1aR, which is critical for AVP binding and may confer increased binding affinity for AVP to Saimiri OTR.

    “Vargas-Pinilla et al. (2015) identified this residue as homologous to Tyr115 in V1aR, which is critical for AVP binding and may confer increased binding affinity for AVP to Saimiri OTR (Chini et al., 1995).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Vargas-Pinilla et al., 2015 source

      Not checked in the free run.

    • cites Chini et al., 1995 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Saimiri, a Pro8-OT species, has a substitution at F103Y, a key residue of the putative binding pocket of OTR.

    “One important exception is in Saimiri. This Pro8-OT species has a substitution at F103Y, which is a key residue of the putative binding pocket of OTR (Gimpl and Fahrenholz, 2001; Vargas-Pinilla et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Gimpl and Fahrenholz, 2001 source

      Not checked in the free run.

    • cites Vargas-Pinilla et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Included in these substitutions are R33Q and N35D.

    “Included in these substitutions are R33Q (a substitution also present in rats, voles, sheep, and cows; Wesley et al., 2002) and N35D.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wesley et al., 2002 source

      Not checked in the free run.

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

    Interpretationreasoning

    The N35D substitution may be a site for altered crosstalk between Pro8-OT and the V2 receptor.

    “Like the F103Y substitution in Saimiri, this vasopressin receptor-like substitution may be a possible site for altered crosstalk between Pro8-OT and the V2 receptor”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Most critical sites for AVP-V1aR binding are conserved, with one notable exception.

    “Like the OTR, most of the critical sites for AVPV1aR binding are conserved (Barberis et al., 1998; Chini et al., 1995; Mouillac et al., 1995; Thibonnier et al., 2000), with one notable exception.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Barberis et al., 1998 source

      Not checked in the free run.

    • cites Chini et al., 1995 source

      Not checked in the free run.

    • cites Mouillac et al., 1995 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A new phosphorylation site in OTR of Callithrix at R149S and shortening of a Ser cluster in OTR of Saguinus important for beta-arrestin mediated desensitization and receptor recycling were identified.

    “Additionally, (Vargas-Pinilla et al., 2015) identified a new phosphorylation site in the OTR of Callithrix at R149S, and the shortening of a Ser cluster in the OTR of Saguinus that is important for β-arrestin mediated desensitization and receptor recycling (Innamorati et al., 1998; Oakley et al., 2001; Vargas-Pinilla et al., 2015).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Vargas-Pinilla et al., 2015 source

      Not checked in the free run.

    • cites Innamorati et al., 1998 source

      Not checked in the free run.

    • cites Oakley et al., 2001 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Experimental truncation of the C-terminus before the palmitoylation site results in reductions in receptor expression, binding affinity, and Ca2+ response, and an overall shift from Gq to Gi coupling.

    “Experimental truncation of the C-terminus before the palmitoylation site results in reductions in receptor expression, binding affinity, and Ca2+ response, and an overall shift from Gq to Gi coupling (Hoare et al., 1999).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Hoare et al., 1999 source

      Not checked in the free run.

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

    Premisenone given

    The SBN includes forebrain and midbrain nuclei and has extensive connectivity with the mesolimbic reward system, which is also rich in neuropeptidergic neurons and receptors.

    “The SBN includes forebrain and midbrain nuclei and has extensive connectivity with the mesolimbic reward system, which is also rich in neuropeptidergic neurons and receptors.”
    Quote in the paperNot a substantial claim

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

    Premisenone given

    V1aR substitutions M381T in Callithrix and N396S in Callicebus each create tripeptide Ser/Thr clusters.

    “For example, the V1aR substitutions M381T in Callithrix and N396S in Callicebus each create tripeptide Ser/Thr clusters.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    O'Connell and Hofmann (2011) proposed that the SBN can be characterized as an integrated social decision-making network that regulates both motivational components of sociality along with adaptive processing of salient social stimuli.

    “O’Connell and Hofmann (2011) proposed that the SBN can be characterized as an integrated social decision-making network that regulates both motivational components of sociality along with adaptive processing of salient social stimuli.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites O’Connell and Hofmann, 2011

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The distribution of OT- and AVP-immunoreactive neurons appears relatively conserved across mammals, with OT-containing neurons in the neurohypophyseal tract (PVN and SON) and AVP-containing neurons in the PVN, SON, and SCN.

    “The distribution of OT- and AVP-immunoreactive (OT-ir; AVP-ir) neurons appear to be relatively conserved across mammals, with OT-containing neurons present in the neurohypophyseal tract (PVN and SON) and AVP-containing neurons present in the PVN, SON, and SCN (Landgraf and Neumann, 2004; Ludwig and Leng, 2006; Sofroniew, 1983).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Landgraf and Neumann, 2004

      Not checked in the free run.

    • cites Ludwig and Leng, 2006 source

      Not checked in the free run.

    • cites Sofroniew, 1983 source

      Not checked in the free run.

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

    Premisenone given

    OTR and V1aR exert their modulatory effect via changes in G protein signaling cascades.

    “As described above in Section 4, OTR and V1aR exert their modulatory effect via changes in G protein signaling cascades.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The distribution of OT-ergic and AVP-ergic neurons and cellular receptors for OT and AVP have been well characterized in rodents and other vertebrates, with substantial overlap with the social behavior network.

    “The distribution of OT-ergic and AVP-ergic neurons, and cellular receptors for OT (OTR) and AVP (V1aR, V1bR, V2R) have been well characterized in rodents (Albers, 2015; Johnson and Young, 2015) and other vertebrates (Goodson and Kabelik, 2009; O’Connell and Hofmann, 2012, 2011), and this distribution includes substantial overlap with the social behavior network (SBN; Newman, 1999).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Albers, 2015 source

      Not checked in the free run.

    • cites Johnson and Young, 2015 source

      Not checked in the free run.

    • cites Goodson and Kabelik, 2009

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    OT- and AVP-containing neurons are mainly localized to the neurohypophyseal tract in primates, but one species of New World monkey expressed OT-ir in extrahypothalamic regions of the SBN.

    “Thus, OT- and AVP-containing neurons are mainly localized to the neurohypophyseal tract in primates, but one species of NWM expressed OT-ir in extrahypothalamic regions of the SBN.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    No extrahypothalamic OT neurons were found in Macaca or Homo, but OT-ir neurons were found in the BNST and meA of Callithrix.

    “However, no extrahypothalamic OT neurons were found in either Macaca or Homo (Caffé et al., 1989; Ishunina and Swaab, 1999), but OT-ir neurons were found in the BNST and meA of Callithrix (Wang et al., 1997a, 1997b).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Caffé et al., 1989 source

      Not checked in the free run.

    • cites Ishunina and Swaab, 1999 source

      Not checked in the free run.

    • cites Wang et al., 1997a, 1997b

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Macaca, dense concentrations of OT fibers were found in the amygdala and NTS, and AVP-ir projected to the amygdala, BNST, PAG, VTA, hippocampus, and NTS, but not the LS.

    “In Macaca, dense concentrations of OT fibers were found in the amygdala and NTS, and AVP-ir was shown to project to the amygdala, BNST, PAG, VTA, hippocampus, and NTS, but not the LS (Caffé et al., 1989).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Caffé et al., 1989 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Among rodents, the LS is a key regulator of social recognition and aggression and expresses high levels of AVP-ir.

    “Among rodents, the LS is a key regulator of social recognition (Everts and Koolhaas, 1997; Lukas et al., 2013) and aggression (Veenema et al., 2010) and expresses high levels of AVP-ir”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Everts and Koolhaas, 1997

      Not checked in the free run.

    • cites Lukas et al., 2013

      Not checked in the free run.

    • cites Veenema et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Callithrix, OT-ir fibers are in the neurohypophyseal tract, BNST, meA, and VMH; AVP-ir fibers are in the neurohypophyseal tract, BNST, and NAcc.

    “In Callithrix, localization studies based on antibodies generated to Leu8-OT revealed OT-ir fibers in the neurohypophyseal tract, BNST, meA, and VMH. AVP-ir fibers were also revealed within the neurohypophyseal tract and BNST, as well as the NAcc.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wang et al., 1997b

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In Callithrix marmosets, there was low but detectable AVP immunoreactivity in the LS, but fibers did not form a dense plexus as in several rodent species.

    “In Callithrix marmosets, there was low, but detectable, AVP immunoreactivity in the LS (confirmed by in situ hybridization; Wang et al., 1997b), but the fibers did not form a dense plexus as found in several rodent species (Caffé et al., 1987; de Vries and Ruijs, 1983).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Wang et al., 1997b

      Not checked in the free run.

    • cites Caffé et al., 1987 source

      Not checked in the free run.

    • cites de Vries and Ruijs, 1983

      Not checked in the free run.

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

    Premisecitation

    Among rodents, there is pronounced interspecific variation in OTR and V1aR binding in the central nervous system that reflects differential social organization and mating strategies.

    “Among rodents, there is pronounced interspecific variation in OTR and V1aR binding in the central nervous system that reflects differential social organization and mating strategies (Barrett et al., 2013; Beery et al., 2008; Insel and Shapiro, 1992; Mooney et al., 2015; Ophir et al., 2012; Young et al., 2011).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Barrett et al., 2013 source

      Not checked in the free run.

    • cites Beery et al., 2008 source

      Not checked in the free run.

    • cites Insel and Shapiro, 1992

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    There are strikingly different profiles for OTR and V1aR across primate species, potentially reflecting species-level differences in social structure and mating strategies as well as phylogeny.

    “There are strikingly different profiles for these receptors across species, potentially reflecting both species-level differences in social structure and mating strategies as well as the secular effects of phylogeny.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In Homo, V1aR was less widely distributed across the social-decision making network relative to Callithrix, Callicebus, and Macaca, although fewer brain regions were sampled.

    “In Homo, V1aR was less widely distributed across the social-decision making network (Loup et al., 1991) relative to Callithrix, Callicebus, and Macaca, although fewer brain regions were sampled.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Loup et al., 1991 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Callicebus does not exhibit OTR binding in the NAcc, and instead densely expresses V1aR.

    “However, Callicebus does not exhibit OTR binding in the NAcc, and instead densely expresses V1aR (confirmed by in situ hybridization; Freeman et al., 2014b).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Freeman et al., 2014b

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Interpretationreasoning

    The drastically different OTR and V1aR expression patterns in Callithrix and Callicebus raise the possibility that OT and AVP systems produce similar social phenotypes via different neural mechanisms.

    “That Callithrix and Callicebus exhibit drastically different expression patterns OTR and V1aR raises the intriguing possibility that OT and AVP systems produce similar social phenotypes via different neural mechanisms.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Callithrix and Callicebus have relatively similar social structures, characterized by high levels of sociality, selective breeding, maintenance of long-term male-female relationships, and biparental care.

    “Callithrix and Callicebus have relatively similar social structures, characterized by high levels of sociality, selective breeding, maintenance of long-term male-female relationships, and biparental care (Digby, 1995; Fernandez-Duque et al., 2009; Spence-Aizenberg et al., 2015).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Digby, 1995 source

      Not checked in the free run.

    • cites Fernandez-Duque et al., 2009 source

      Not checked in the free run.

    • cites Spence-Aizenberg et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    OTRs are less widely and densely distributed, but include expression in hypothalamic nuclei, NAcc, VP, LS, and hippocampus.

    “OTRs are less widely and densely distributed, but include expression in hypothalamic nuclei, NAcc, VP, LS, and hippocampus.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    V1aR in sensory areas in Macaca and Homo are much less widespread, and was only found in V1 in Macaca.

    “V1aR in sensory areas in Macaca and Homo are much less widespread, and was only found in V1 in Macaca.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    In Callithrix and Callicebus, V1aR expression is less widespread, but is apparent across several critical sensory processing centers.

    “In Callithrix and Callicebus, V1aR expression is less widespread, but is apparent across several critical sensory processing centers.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationreasoning

    Across New World, Old World, and hominid primates, cellular receptors for OT and AVP are widely distributed across the social-decision making network, but there is pronounced variation in presence and density of OTR and V1aR, potentially guiding important differences in social phenotype.

    “In sum, across a sampling of New World, Old World, and hominid primates, cellular receptors for OT and AVP are widely distributed across the social-decision making network, but there is pronounced variation in the presence and density of OTR and V1aR, potentially guiding important differences in social phenotype.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Initiating and maintaining visual contact with another individual is a critical prerequisite for navigating the social environment, establishing and maintaining dominance hierarchies, as well developing long-term social bonds and cooperative relationships.

    “In particular, initiating and maintaining visual contact with another individual is a critical prerequisite for navigating the social environment, establishing and maintaining dominance hierarchies, as well developing long-term social bonds and cooperative relationships.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Callicebus show binding for V1aR in the SC and V1; V1aR binding for the NTS, NBM, or OB was not reported.

    “Callicebus show binding for V1aR in the SC and V1; V1aR binding for the NTS, NBM, or OB was not reported (Freeman et al., 2014b).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Freeman et al., 2014b

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Macaca showed no V1aR binding in the SC, and Homo showed no V1aR binding in either the SC or NBM.

    “Macaca showed no V1aR binding in the SC, and Homo showed no V1aR binding in either the SC or NBM (Freeman et al., 2014a; Loup et al., 1991).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Freeman et al., 2014a

      Not checked in the free run.

    • cites Loup et al., 1991 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Binding of labeled OT in Homo was shown across the social-decision making network, but was notably absent from the NAcc and hippocampus, similar to Callithrix.

    “Interestingly, binding of labeled OT in Homo was shown across the social-decision making network, but was notably absent from the NAcc and hippocampus (Boccia et al., 2013; Loup et al., 1991, 1989), similar to Callithrix.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Boccia et al., 2013 source

      Not checked in the free run.

    • cites Loup et al., 1991, 1989

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Premisenone given

    In human and non-human primates, processing of social information is largely guided by visual and auditory systems, and to a lesser extent olfactory systems.

    “In human and non-human primates, processing of social information is largely guided by the visual and auditory systems (and to a lesser extent, olfactory systems).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Callithrix show dense binding for V1aR in the NTS and OB, with moderate binding in the NBM; V1aR binding for the SC or V1 was not reported.

    “Callithrix show dense binding for V1aR in the NTS and OB, with moderate binding in the NBM; V1aR binding for the SC or V1 was not reported (Schorscher-Petcu et al., 2009; Wang et al., 1997b).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Schorscher-Petcu et al., 2009 source

      Not checked in the free run.

    • cites Wang et al., 1997b

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The NTS and V1 also show positive binding for OTR in primates, but OTR expression in these regions is not consistently reported across studies.

    “The NTS and V1 also show positive binding for OTR in primates, but OTR expression in these regions is not consistently reported across these studies.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Premisenone given

    No data are available regarding sex differences in the central distribution of OTR in non-human primates.

    “No data are available regarding sex differences in the central distribution of OTR in non-human primates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OT system parameters also differ between males and females in some species of rodents, with males having more OT-ir neurons/fibers and greater OTR density and distribution in some species and females having higher OT system parameters in other species.

    “OT system parameters also differ between males and females in some species of rodents, with males having more OT-ir neurons/fibers and greater OTR density and distribution in some species and females having higher OT system parameters in other species (see Dumais and Veenema, 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dumais and Veenema, 2015

      Not checked in the free run.

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

    Premisecitation

    The sexually dimorphic nature of AVP, and to a lesser extent OT, in the rodent brain is fairly well characterized.

    “The sexually dimorphic nature of AVP, and to a lesser extent OT, in the rodent brain is fairly well characterized, (De Vries and Panzica, 2006; Dumais and Veenema, 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites De Vries and Panzica, 2006

      Not checked in the free run.

    • cites Dumais and Veenema, 2015

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Generally, OT and AVP system parameters are not different between males and females across rodents, with no detectable differences in the neurohypophyseal tract and hypothalamic nuclei.

    “Generally, OT and AVP system parameters are not different between males and females across rodents, with no detectable differences in the neurohypophyseal tract and hypothalamic nuclei (see Dumais and Veenema, 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dumais and Veenema, 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    These results suggest an important modulatory role of neuropeptides, particularly OT, in processing visual and multimodal social stimuli among all primates, and an important role for AVP in these processes in Callithrix.

    “These results suggest an important modulatory role of neuropeptides (particularly OT) in processing visual (e.g., facial recognition, directing eye gaze) and multimodal social stimuli among all primates, and an important role for AVP in these processes in Callithrix.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Sex differences in central OT and AVP system parameters appear to be species- and brain region-specific, and these differences likely contribute in part to differences in social behavior across and within species.

    “Thus, sex differences in central OT and AVP system parameters appear to be species- and brain region-specific, and these differences likely contribute in part to differences in social behavior across and within species.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisereasoning

    OT and AVP are known to regulate social behavior in sex-specific ways, which is likely regulated in part by sex differences in OT and AVP synthesis and in density and distribution of OTR and V1aR in the brain.

    “OT and AVP are known to regulate social behavior in sex-specific ways, which is likely regulated in part by sex differences in OT and AVP synthesis and in the density and distribution of OTR and V1aR in the brain.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The important role of neuropeptide signaling in regulating a host of behavioral processes in invertebrate and especially vertebrate animals, especially in the social realm, has been firmly established.

    “The important role of neuropeptide signaling in regulating a host of behavioral processes in invertebrate and especially vertebrate animals, especially in the social realm, has been firmly established (Albers, 2015; Caldwell and Young III, 2006; Donaldson and Young, 2008; Taghert and Nitabach, 2012; Wircer et al., 2015).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Albers, 2015 source

      Not checked in the free run.

    • cites Caldwell and Young III, 2006

      Not checked in the free run.

    • cites Donaldson and Young, 2008 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Squirrel monkeys and capuchins exhibit non-monogamous social systems.

    “Squirrel monkeys and capuchins, conversely, exhibit non-monogamous social systems.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Boinski, 1987 source

      Not checked in the free run.

    • cites Fedigan, 1993 source

      Not checked in the free run.

    • cites Janson, 1986

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Titi and owl monkeys show similar patterns of behavior to callitrichines, but exhibit less extra-pair interactions and hence are more socially monogamous than most callitrichines.

    “Other NWM such as titi and owl monkeys show similar patterns of behavior, but exhibit less extra-pair interactions and hence are ‘more’ socially monogamous than most callitrichines (Díaz-Muñoz and Bales, 2016; Fernandez-Duque, 2007; Spence-Aizenberg et al., 2015).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Díaz-Muñoz and Bales, 2016

      Not checked in the free run.

    • cites Fernandez-Duque, 2007

      Not checked in the free run.

    • cites Spence-Aizenberg et al., 2015

      Not checked in the free run.

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

    Premisecitation

    Capuchins exhibit multi-male/multi-female hierarchical social organization.

    “capuchins exhibit multi-male/multi-female hierarchical social organization”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Fedigan, 1993 source

      Not checked in the free run.

    • cites Janson, 1986

      Not checked in the free run.

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

    Premisecitation

    Squirrel monkeys live in large mixed-sex groups and exhibit seasonal sexual dimorphism.

    “Squirrel monkeys live in large mixed-sex groups and exhibit seasonal sexual dimorphism”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Boinski, 1987 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Females treated with Pro8-OT drastically reduced their time spent with a stranger in favor of interacting with their partner, while males treated with Pro8-OT spent less time with both the stranger and their partner.

    “Females treated with Pro8-OT drastically reduced their time spent with a stranger in favor of interacting with their partner, while males treated with Pro8-OT spent less time with both the stranger and their partner (Cavanaugh et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The effect of IN Pro8-OT on partner/stranger preferences was specific to the Pro8-OT variant, as treatment with Leu8-OT did not alter partner/stranger preferences.

    “This effect was specific to the Pro8-OT variant, as treatment with Leu8-OT did not alter partner/stranger preferences.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Female marmosets initiated and maintained proximity more often when their mate was treated with IN OT compared to when their mate was treated with a saline control, suggesting that OT makes male marmosets more socially attractive.

    “Female marmosets initiated and maintained proximity more often when their mate was treated with IN OT compared to when their mate was treated with a saline control, suggesting that OT makes male marmosets more ‘socially attractive’ (Cavanaugh et al., 2015).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    IN OT enhances social contact and affiliation with mates and inhibits sociality toward strangers.

    “IN OT enhances social contact and affiliation with mates and inhibits sociality toward strangers.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Treatment with IN Pro8-OT facilitated fidelity with a long-term partner by decreasing the amount of time marmosets spent in close proximity with an opposite-sex stranger, and increasing the latency to exhibit sociosexual behavior toward a stranger in a partner-preference paradigm.

    “Treatment with IN Pro8-OT facilitated fidelity with a long-term partner by decreasing the amount of time marmosets spent in close proximity with an opposite-sex stranger, and increasing the latency to exhibit sociosexual behavior toward a stranger in a partner-preference paradigm (Cavanaugh et al., 2014).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2014 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Neuropeptide treatment (OT in marmosets, AVP in titi monkeys) both reduced interest in extrapair partners and enhanced sociality toward pairmates.

    “neuropeptide treatment (OT in the case of marmosets, AVP in the case of titi monkeys) both reduced interest in extrapair partners and enhanced sociality toward pairmates.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Compared to non-fathers, both first-time and experienced marmoset fathers have increased vasopressin V1aR density in neurons in the prefrontal cortex, as well as increases in the proportion of dendritic spines with V1aR.

    “Compared to non-fathers, both first-time and experienced marmoset fathers have increased vasopressin V1aR density in neurons in the prefrontal cortex, as well as increases in the proportion of dendritic spines with V1aR (Kozorovitskiy et al., 2006).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Kozorovitskiy et al., 2006 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The presence of a mate during a stressor significantly attenuated HPA-axis activity in female marmosets, but not males, relative to when marmosets experienced a stressor in complete isolation.

    “The presence of a mate during a stressor significantly attenuated HPA-axis activity in females, but not males, relative to when marmosets experienced a stressor in complete isolation.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Blocking OT signaling in marmosets with an OTa led to significantly higher cortisol levels in males during the stressor, suggesting that OT may reduce the stress-induced elevations in cortisol levels.

    “blocking OT signaling in marmosets with an OTa led to significantly higher cortisol levels in males during the stressor, suggesting that OT may reduce the stress-induced elevations in cortisol levels.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Cavanaugh et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Untreated marmosets, tamarins, and capuchins have each demonstrated some form of spontaneous other-regarding preferences toward familiar partners.

    “Untreated marmosets (Burkart et al., 2007), tamarins (Cronin et al., 2010), and capuchins (Lakshminarayanan and Santos, 2008) have each demonstrated some form of spontaneous other-regarding preferences toward familiar partners”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Burkart et al., 2007 source

      Not checked in the free run.

    • cites Cronin et al., 2010 source

      Not checked in the free run.

    • cites Lakshminarayanan and Santos, 2008

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Parental care is affected by experimentally modifying neuropeptide concentrations, and engaging in parental care (at least paternal care) serves as a potent stimulus to alter both neuropeptide synthesis and release, and receptor expression.

    “parental care is affected by experimentally modifying neuropeptide concentrations, and engaging in parental care (at least paternal care) serves as a potent stimulus to alter both neuropeptide synthesis and release, and receptor expression.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OT mediates mother-infant attachments via both physiological mechanisms (e.g., uterine contraction, milk-let down) and behavioral mechanisms (e.g., mother-infant bonding).

    “OT mediates mother-infant attachments via both physiological mechanisms (e.g., uterine contraction, milk-let down) and also behavioral mechanisms (e.g., mother-infant bonding; (Rilling and Young, 2014).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Rilling and Young, 2014 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Marmosets treated with IN Pro8-OT reduced altruistic food sharing with opposite-sex strangers, but altruistic food sharing with their long-term pairmates was unaffected.

    “marmosets treated with IN Pro8-OT reduced ‘altruistic’ food sharing with opposite-sex strangers, but ‘altruistic’ food sharing with their long-term pairmates was unaffected.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mustoe et al., 2015 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    Studies examining the effects of neuropeptides on social behavior in NWM repeatedly demonstrate that neuropeptides do not universally enhance sociality and, in some cases, neuropeptides like OT have no significant influence on socially-relevant behavior.

    “neuropeptides do not universally enhancing sociality and, in some cases, neuropeptides like OT have no significant influence on socially-relevant behavior (Mustoe et al., 2016).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Mustoe et al., 2016 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    Most studies using IN neuropeptides administer large doses that represent supraphysiological concentrations of neuropeptides, at least in the periphery, and doses are not always consistent across studies.

    “Most studies using IN neuropeptides administer large doses that represent supraphysiological concentrations of neuropeptides, at least in the periphery, and doses are not always consistent across studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductreasoning

    Studies reported herein that map the distribution of oxytocinergic neurons and localize the OTR in Callithrix were conducted prior to the discovery of Pro8-OT in this species, and hence used antibodies and labeled agonists or antagonists optimized for species with Leu8-OT.

    “studies reported herein that map the distribution of oxytocinergic neurons and localize the OTR in Callithrix were conducted prior to the discovery of Pro8-OT in this species, and hence used antibodies and labeled agonists or antagonists optimized for species with Leu8-OT.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    OT and AVP do not abundantly or easily penetrate the blood brain barrier, and it is estimated based on previous studies that, at best, only 0.005% of the IN administered neuropeptides accumulate in CSF within an hour.

    “OT and AVP do not abundantly or easily penetrate the blood brain barrier, and it is estimated based on previous studies that, at best, only 0.005% of the IN administered neuropeptides accumulate in CSF within an hour (Leng and Ludwig, 2015).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Leng and Ludwig, 2015

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    This review has identified important variation in the cognate receptors for OT and AVP in NWM, in ways that are linked to both ligand variation (in the case of OTR) and with social structure (in the case of V1aR).

    “This review has also identified important variation in the cognate receptors for OT and AVP in NWM, in ways that are linked to both ligand variation (in the case of OTR) and with social structure (in the case of V1aR).”
    Quote in the paperSubstantial claim
121 of 121

  • The paper relies on this without support.

    OT is a critical mediator for placental birth and lactation in eutherian mammals.

    “OT is a critical mediator for two of the fundamental defining reproductive characteristics of eutherian mammals: placental birth and lactation.”

  • The paper relies on this without support.

    Titi monkeys are socially monogamous and exhibit biparental cooperation, but express the Leu8-OT ligand.

    “For instance, titi monkeys are socially monogamous and exhibit biparental cooperation, but express the Leu8-OT ligand.”

  • The paper relies on this without support.

    Squirrel monkeys and capuchins are non-monogamous and uniparental, yet both possess the Pro8-OT ligand.

    “Conversely, squirrel monkeys and capuchins are non-monogamous and uniparental, yet both possess the Pro8-OT ligand.”

  • The paper relies on this without support.

    NWM are important models for social behavior because many species show intraspecific and idiosyncratic variability in behaviors translatable to humans including pair-bonding, biparental care, and high levels of cooperation and aggression.

    “NWM are important models for social behavior because many species show intraspecific and idiosyncratic variability in behaviors that are translatable to humans including pair-bonding, biparental care, and high levels of cooperation and aggression.”

  • The paper relies on this without support.

    The conserved function of nonapeptides can be made manifest via alternative phenotypic routes.

    “The notion that the conserved function of nonapeptides can be made manifest via alternative phenotypic routes”
5 of 5

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?

  • 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).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [68]

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.

  • Human NAcc binding is incorrectly described as similar to Callithrix

    Minor

    The paper says Callithrix has dense OTR expression in the NAcc, but later calls the absence of labeled OT binding in the human NAcc similar to Callithrix.

  • The ligand specificity of the two marmoset effects is reversed

    Minor

    Partner preference is described as specific to Pro8-OT, while the later effect is described as similar under Pro8-OT and Leu8-OT. The later sentence nevertheless calls that effect ligand-specific and says it differs from the partner-preference result.

  • The position-8 codon substitution is given in opposite directions

    Minor

    The first passage gives CCG → CTG as the substitution producing proline at position 8. The later passage gives the reverse substitution, CTG → CCG, as producing proline at that position.

3 of 3

The citation lists haven’t been fetched yet

References 203 · Cited by 66

Research works printed but not linked: 1

  1. Janson, 1986, The mating system as a determinant of social evolution in capuchin monkeys (Cebus), Primate Ecol. Conserv., 2, 169

Authors
French, J. A., Taylor, J. H., Mustoe, A. C., & Cavanaugh, J.
Affiliations
University of Nebraska at Omaha (US)
Corresponding author
French, Jeffrey A.
ORCID
Venue
Frontiers in Neuroendocrinology
Publisher
Elsevier BV
Published
2016-07
Volume
42
Pages
18-39
ISSN
0091-3022 (ISSN-L)
DOI
10.1016/j.yfrne.2016.03.004
PMC
PMC5030117
OpenAlex
W2306727439
Semantic Scholar
17456c2177ec1a6024417035904af35a41493207
Cited by
66
References
203
Citations by year
2026: 6 · 2025: 4 · 2024: 2 · 2023: 1 · 2022: 8 · 2021: 3 · 2020: 22 · 2019: 4 · 2018: 8 · 2017: 5 · 2016: 3
FWCI
1.04
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Frontiers in Neuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (HD042882)
  • Nebraska Foundation
  • Office of Research and Creative Activity at UNO
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Social Sciences › Psychology › Social Psychology › Primate Behavior and Ecology
Keywords
oxytocin, vasopressin, oxytocin receptor, vasopressin V1a receptor, New World monkeys, social behavior, ligand evolution, primate brain, sociality
MeSH terms
Animals, Behavior, Animal, Brain, Oxytocin, Primates, Social Behavior, Vasopressins, Receptors, Vasopressin, 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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