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Cited by 157Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyNeurotransmitter Receptor Influence on Behavior

Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

Open access
Bredewold, Remco, Smith, Caroline J. W., Dumais, Kelly M., Veenema, Alexa H.·2014·Frontiers in Behavioral Neuroscience
DOI 10.3389/fnbeh.2014.00216PMC PMC4058593
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Abstract

We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me(2))AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5-[Tyr(Me)(2),Thr(4)]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.

AI snapshot

Written from the paper’s full text.

TL;DR

In juvenile rats, vasopressin and oxytocin manipulations in the lateral septum modulate social play in sex- and social-context-specific ways. V1aR blockade increased home-cage play in males but reduced it in females, while AVP reduced novel-cage play in females and OXT reduced home-cage play in females.

Key findings

  • V1aR antagonist in the lateral septum enhanced home-cage social play in males but reduced it in females; these effects were absent in the novel cage. Social play showed a treatment × sex × context effect, F(2, 104) = 3.96, p < 0.05, with a significant treatment × sex effect in the home cage only, F(2, 53) = 15.3, p < 0.001.
  • AVP treatment reduced social play in females in the novel cage (p < 0.05 vs. vehicle-treated females) but not in the home cage. AVP also increased anxiety-like behavior in males on the elevated plus-maze, with less open-arm time and fewer open-arm entries than vehicle-treated males (p < 0.01 for both), but did not do so in females.
  • OXT treatment reduced social play in females only in the home cage (p < 0.005 vs. vehicle-treated females; p < 0.01 vs. OTR antagonist-treated females). OTR antagonist treatment did not alter social play overall, but OTR-A-treated females showed less social play in the novel vs. home cage (p < 0.05).
  • Vehicle-treated male and female rats did not differ in social play behaviors. OTR-A and OXT treatments did not alter anxiety-like behavior or locomotion on the elevated plus-maze.

Methods

  • Juvenile male and female Wistar rats were obtained at 23 days of age, cannulated at 30–31 days, and tested for social play 3 and 5 days after surgery in home and novel cages in counterbalanced order with an age- and sex-matched unfamiliar rat for 10 min. A separate set was tested on the elevated plus-maze 3 days after surgery.
  • Rats received lateral septum microinjections 20 min before testing: vehicle Ringer’s solution, V1aR antagonist d(CH2)5[Tyr(Me)2]AVP (10 ng/0.5 μl), AVP (200 pg/0.5 μl), OTR antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT (10 ng/0.5 μl), or OXT (200 pg/0.5 μl).
  • Social play was analyzed with a three-way ANOVA (sex × treatment × context) followed by Bonferroni post-hoc tests, two-way ANOVAs, or one-way ANOVAs; elevated plus-maze behavior was analyzed with a two-way ANOVA (sex × treatment) followed by Bonferroni post-hoc tests. Significance was set at p < 0.05.

Limitations

  • The paper states that higher drug doses might have been effective in altering home-cage social play, and that endogenous AVP may already influence social play at maximum levels. It also notes that future studies administering receptor antagonists prior to the neuropeptide are needed to confirm that AVP and OXT act via their own receptors.
  • The paper states that determining the release patterns of OXT and AVP during social play would further help define their involvement in sex- and context-specific modulation.
  • Evident from the text: the study uses one dose per drug, one brain region (lateral septum), one rat strain and age, and brief 10-min social play tests; it does not directly measure endogenous AVP/OXT release during behavior.

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

Integrity signals

Registry

Crossref · 10.3389/fnbeh.2014.00216

Cites

79 of 79 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

26 of 77 cited sources checked · 13 supported · 1 flagged · accuracy not yet measured

  • Interpretationcitation

    It is less likely that AVP and OXT may have acted via each other's receptors.

    “Additionally, the neuropeptide- and receptor antagonist-specific effects on social play suggests that it is less likely that AVP and OXT may have acted via each other's receptors (Chini and Manning, 2007; Schorscher-Petcu et al., 2010).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Chini and Manning, 2007 source
    • cites Schorscher-Petcu et al., 2010 source

      The Introduction states that both OXT and AVP can activate both receptors. More decisively, the Results (Oxytocin and vasopressin 1a receptor antagonists) report that a V1AR antagonist prevented OXT-induced analgesia, supporting OXT action through AVP’s receptor rather than making cross-receptor action unlikely. The paper studies analgesia, not social play. (LLM, conf=0.83)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    A negative correlation was found between AVP mRNA expression in the bed nucleus of the stria terminalis and social play in juvenile males.

    “In line with this, a negative correlation was found between AVP mRNA expression in the bed nucleus of the stria terminalis and social play in juvenile males (Paul et al., 2014).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Paul et al., 2014 source

      Experiment 2 reports a significant negative correlation between BNST AVP mRNA and play in male rats aged 18 and 21 days. The Discussion distinguishes the weanlings tested in this study from juveniles tested in another study, so “juvenile males” is broader than the study population. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
  • Premisecitation

    Social play activities were found to be altered in juvenile male rats that were exposed to either maternal separation or prenatal immune stress.

    “Likewise, social play activities were found to be altered in juvenile male rats that were exposed to either maternal separation (Veenema and Neumann, 2009) or prenatal immune stress (Taylor et al., 2012).”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Veenema and Neumann, 2009 source
    • cites Taylor et al., 2012 source
  • Premisecitation

    The lateral septum serves as a hub in the brain by integrating social, emotional, and contextual information from different brain systems and contributing to the coordination of adaptive context-specific behavioral responses.

    “this area serves as a hub in the brain by integrating social, emotional, and contextual information from different brain systems and contributing to the coordination of adaptive context-specific behavioral responses (Sheehan et al., 2004; Luo et al., 2011)”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Sheehan et al., 2004 source
    • cites Luo et al., 2011 source

      The paper describes the lateral septum as a relay carrying contextual information from hippocampal CA3 to the VTA, and reports that this pathway contributes to context-induced cocaine-seeking (Abstract; no page supplied). It does not establish that the lateral septum integrates social and emotional information from multiple brain systems or serves as a general hub for adaptive behavior. (LLM, conf=0.87)

      Experimental — accuracy not yet measured
  • Premisecitation

    V1aR and OTR are abundantly expressed in the lateral septum in juvenile rats.

    “V1aR and the OTR are abundantly expressed in this area in juvenile rats (Lukas et al., 2010; Veenema et al., 2012)”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites Lukas et al., 2010 source
    • cites Veenema et al., 2012 source

      The Discussion reports abundant septal V1aR binding densities in both male and female juvenile rats. Our copy does not establish abundant OTR expression in the juvenile lateral septum, so it supports only the V1aR part of the claim. The indexed passages provide no page number. (LLM, conf=0.91)

      Experimental — accuracy not yet measured
  • May combine two claims. 15
  • Classified as probably not a substantial claim. 18

  • May combine two claims.

    Premisecitation

    Pharmacological blockade of AVP V1a receptors in the lateral septum increased social play in juvenile males while it reduced social play in juvenile females.

    “Indeed, we recently showed that pharmacological blockade of AVP V1a receptors in the lateral septum increased social play in juvenile males while it reduced social play in juvenile females (Veenema et al., 2013).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Veenema et al., 2013 source

  • May combine two claims.

    Premisecitation

    Males have more AVP-expressing cells in the bed nucleus of the stria terminalis and medial amygdala and denser AVP-axonal projections to limbic brain regions, especially to the lateral septum.

    “For example, males have more AVP-expressing cells in the bed nucleus of the stria terminalis and medial amygdala and denser AVP-axonal projections to limbic brain regions, especially to the lateral septum (De Vries et al., 1981; Van Leeuwen et al., 1985; Szot and Dorsa, 1993).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites De Vries et al., 1981 source

      The Discussion (p. 9) reports denser AVP-containing fibers in male rats in the lateral septum and, to a lesser extent, the lateral habenular nucleus. It does not establish that males have more AVP-expressing cells in the bed nucleus of the stria terminalis or medial amygdala; the cells studied were in the suprachiasmatic nucleus. (LLM, conf=0.89)

      Experimental — accuracy not yet measured
    • cites Van Leeuwen et al., 1985 source
    • cites Szot and Dorsa, 1993 source

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

    Premisecitation

    Social play activities seem to contribute to the development of social and emotional skills needed throughout life, as shown in humans, non-human primates, and rodents.

    “These social play activities seem to contribute to the development of social and emotional skills needed throughout life, as shown in humans, non-human primates, and rodents (Sigman and Ruskin, 1999; Guralnick et al., 2006; Cordoni and Palagi, 2011).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Sigman and Ruskin, 1999 source
    • cites Guralnick et al., 2006 source
    • cites Cordoni and Palagi, 2011 source

      The Introduction (page not available) says infant play helps children and non-human primates acquire social competence; the Discussion also links play signals to emotional regulation in primates. Our copy does not extend the developmental claim to rodents or establish that the skills are needed throughout life. (LLM, conf=0.85)

      Experimental — accuracy not yet measured

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

    Premisecitation

    Both AVP and OXT have been implicated in ASD and other social disorders and are currently being tested in clinical trials.

    “since both neuropeptides have been implicated in ASD and other social disorders (Meyer-Lindenberg et al., 2011; Modi and Young, 2012) and are currently being tested in clinical trials (clinicaltrials.gov).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Meyer-Lindenberg et al., 2011 source
    • cites Modi and Young, 2012 source

      The Introduction links oxytocin to ASD and other psychiatric disorders with social impairments. The Social information processing and recognition section also describes a possible alteration of both oxytocin and vasopressin systems in ASD, but does not establish vasopressin’s involvement in the other disorders. The clinical-trials clause is cited to clinicaltrials.gov, not to Modi and Young. (LLM, conf=0.83)

      Experimental — accuracy not yet measured
    • cites clinicaltrials.gov

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

  • May combine two claims.

    Premisecitation

    The injection site was chosen because it is positioned centrally in the region where males and females express high densities of V1aR and OTR binding in the lateral septum and corresponds with previous studies showing that pharmacological manipulations of AVP and OXT systems in the rat lateral septum altered social behavior.

    “This injection site was chosen because it is positioned centrally in the region where males and females express high densities of V1aR and OTR binding in the lateral septum (Lukas et al., 2010; Veenema et al., 2012; Figure 1) and because the injection site corresponds with previous studies showing that pharmacological manipulations of AVP and OXT systems in the rat lateral septum altered social”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Lukas et al., 2010 source
    • cites Veenema et al., 2012 source

      Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

      Experimental — accuracy not yet measured
    • cites Veenema et al., 2010 source

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

    Premisecitation

    Central blockade of the V1aR reduces aggression in dominant male violet-eared waxbills toward an unfamiliar male during mate competition aggression but not during resident-intruder aggression.

    “For example, central blockade of the V1aR reduces aggression in dominant male violet-eared waxbills toward an unfamiliar male during mate competition aggression but not during resident-intruder aggression (Goodson et al., 2009).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Goodson et al., 2009 source

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

    Premisecitation

    Blockade of the vasoactive intestinal polypeptide receptor in the brain of zebra finches alters social contact behavior in a novel, but not familiar, environment.

    “Moreover, blockade of the vasoactive intestinal polypeptide receptor in the brain of zebra finches alters social contact behavior in a novel, but not familiar, environment (Kingsbury et al., 2013).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Kingsbury et al., 2013 source

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

    Premisecitation

    Social play is a highly motivational behavior.

    “Social play is a highly motivational behavior (Trezza et al., 2010)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Trezza et al., 2010 source

  • May combine two claims.

    Premisecitation

    The same dose of AVP altered novel cage social play behavior in females, anxiety-related behavior in males, and social recognition in both male and female juvenile rats.

    “However, the same dose of AVP altered novel cage social play behavior in females, anxiety-related behavior in males, and social recognition in both male and female juvenile rats (Veenema et al., 2012).”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Veenema et al., 2012 source

      The Results (Experiment 3; page not provided) report that the 200 pg AVP dose increased social preference in juvenile females, but not juvenile males. The paper does not report a novel-cage social-play test or an AVP-dose effect on anxiety in male rats; its Discussion mentions anxiety-related behavior only in a separate mouse knockout study. (LLM, conf=0.90)

      Experimental — accuracy not yet measured

  • May combine two claims.

    Findingown data

    AVP enhanced anxiety-related behavior in males tested on the elevated plus-maze, but failed to do so in females.

    “AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms.”
    • Also stated in: § Modulation of non-social anxiety-like behavior by AVP · plain
      “AVP treatment altered anxiety in sex-specific ways as reflected by treatment x sex effects for percentage time on open arms [F(2, 51) = 3.41, p < 0.05] and percentage open arm entries [F(2, 51) = 7.39, p < 0.05].”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    V1aR-A treatment in the home cage enhanced the number of pins in males while it reduced the number of pins in females.

    “V1aR-A treatment in the home cage enhanced the number of pins in males (p < 0.05 vs. vehicle-treated and p < 0.001 vs. AVP-treated males, Figure 2C) while it reduced the number of pins in females (p < 0.05 vs. vehicle-treated females, Figure 2C).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    AVP-treated males spent less time on the open arms and had less open arm entries than AVP-treated females.

    “Furthermore, AVP-treated males spent less time on the open arms (p < 0.05, Figure 4A) and had less open arm entries (p < 0.005, Figure 4B) than AVP-treated females.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    AVP-treated males spent less time on the open arms and had less open arm entries than vehicle-treated males.

    “AVP-treated males spent less time on the open arms (Figure 4A) and had less open arm entries (Figure 4B) than vehicle-treated males (time: p < 0.01; entries: p < 0.01) and V1aR-A-treated males (entries: p < 0.005).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    OXT decreased social play behavior in females in the home but not in the novel cage.

    “Last, OXT decreased social play behavior in females in the home but not in the novel cage.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    AVP and OXT, acting on the lateral septum, may modulate social behavior, and possibly juvenile social play, in sexually dimorphic ways.

    “These findings suggest that AVP and OXT, acting on, e.g., the lateral septum, may modulate social behavior, and possibly juvenile social play, in sexually dimorphic ways.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Sex and social context are important factors to consider in how AVP and OXT modulate social play behavior and, most likely, other social behaviors as well.

    “These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.”
    • Also stated in: § Discussion · hedged
      “These findings indicate that sex and social context are important factors to consider in how AVP and OXT modulate social play behavior and, most likely, other social behaviors as well.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Social play is predominantly displayed among juveniles of both sexes across many mammalian species.

    “Social play (also referred to as play-fighting or rough-and-tumble play) is predominantly displayed among juveniles of both sexes across many mammalian species (Bekoff and Byers, 1998; Pellis and Iwaniuk, 2000; Burghardt, 2005).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Bekoff and Byers, 1998

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

    • cites Pellis and Iwaniuk, 2000 source
    • cites Burghardt, 2005 source

  • Classified as probably not a substantial claim.

    Premisecitation

    AVP and OXT have robust neuromodulatory effects on adult social behavior, including aggression, social recognition, and pair-bonding.

    “AVP and OXT have robust neuromodulatory effects on adult social behavior, including aggression, social recognition, and pair-bonding (Donaldson and Young, 2008; Veenema and Neumann, 2008; Goodson and Thompson, 2010)”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Donaldson and Young, 2008 source
    • cites Veenema and Neumann, 2008 source
    • cites Goodson and Thompson, 2010 source

  • May combine two claims.

    Premisecitation

    AVP typically enhances while OXT reduces anxiety-like behaviors of rats exposed to novel environments.

    “Because AVP typically enhances (Landgraf et al., 1995; Beiderbeck et al., 2007) while OXT reduces (Windle et al., 1997; Ring et al., 2006; Blume et al., 2008) anxiety-like behaviors of rats exposed to novel environments”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Landgraf et al., 1995 source
    • cites Beiderbeck et al., 2007 source
    • cites Windle et al., 1997 source

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

    Premisecitation

    The elevated plus-maze is based on the rat's natural conflict between its exploratory drive and its innate fear of elevated, open and novel spaces.

    “The elevated plus-maze is based on the rat's natural conflict between its exploratory drive and its innate fear of elevated, open and novel spaces (Pellow et al., 1985).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pellow et al., 1985 source

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Proper placement of cannulae into the lateral septum was verified histologically using charcoal injection on Nissl-stained coronal brain sections.

    “At the end of the experiments, rats were killed with CO2, and charcoal was injected as a marker to check proper placement of the cannulae into the lateral septum histologically on Nissl-stained coronal brain sections.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Rats were tested once in the home cage and once in a novel cage in counterbalanced order.

    “The first set of rats was tested for social play 3 and 5 days after surgery, once in the home cage and once in a novel cage in counterbalanced order, and given the same drug.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductown data

    Social play tests were videotaped and analyzed by a researcher blind to the treatment condition.

    “All tests were videotaped for subsequent analysis of behavior by a researcher blind to the treatment condition using JWatcher”
    • Also stated in: § Elevated plus-maze test · plain
      “Behavior was measured by means of a video camera mounted above the maze and scored in an adjacent room by a researcher blind to the treatment condition using JWatcher.”
    Quote in the paperSubstantial claim

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

    Premisecitation

    Sex-specific responses to AVP and OXT manipulations in rodents have been reported for behaviors other than juvenile social play, including aggression, partner preference, alloparental behavior, and social recognition.

    “Sex-specific responses to AVP and OXT manipulations in rodents have been reported for behaviors other than juvenile social play, including aggression (Ferris and Potegal, 1988; Gutzler et al., 2010), partner preference (Insel and Hulihan, 1995; Cho et al., 1999; Bales et al., 2013), alloparental behavior (Bales et al., 2004), and social recognition (Bluthé and Dantzer, 1990; Engelmann et al., 1998”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Ferris and Potegal, 1988 source
    • cites Gutzler et al., 2010 source
    • cites Insel and Hulihan, 1995 source

  • May combine two claims.

    Interpretationcitation

    OXT has a modulatory role in responding to the salience and/or valence of social stimuli, likely facilitating affiliative responses to positive social stimuli and anxiogenic responses to negative social stimuli.

    “These findings suggests that OXT has a modulatory role in responding to the salience and/or valence of social stimuli, likely facilitating affiliative responses to positive social stimuli and anxiogenic responses to negative social stimuli.”
    Quote in the paperSubstantial claim

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

    Study design and conductnone given

    Higher drug doses than those used cannot be excluded as potentially effective in altering social play behavior in the home cage.

    “We cannot exclude that higher drug doses would be effective in altering social play behavior in the home cage.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    The bed nucleus of the stria terminalis shows denser OTR binding than the lateral septum.

    “an area that shows denser OTR binding than the lateral septum (Dumais et al., 2013a).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dumais et al., 2013a source

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

    Interpretationreasoning

    Social context-dependent input from the hippocampus to the lateral septum may have modulated the ability of AVP and OXT systems to alter lateral septum activity resulting in context-specific effects of V1aR antagonist, AVP, OTR antagonist, and OXT treatments on social play behavior.

    “In this scenario, social context-dependent input from the hippocampus to the lateral septum may have modulated the ability of AVP and OXT systems to alter lateral septum activity resulting in context-specific effects of V1aR antagonist, AVP, OTR antagonist, and OXT treatments on social play behavior.”
    Quote in the paperNot a substantial claim

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

    Interpretationcitation

    A possible circuit could comprise the hippocampus transmitting contextual information onto the lateral septum which, in turn, relays this information onto areas such as the lateral hypothalamus and the ventral tegmental area to modulate behavioral responses appropriate to particular environmental stimuli.

    “A possible circuit could comprise the hippocampus transmitting contextual information onto the lateral septum which, in turn, relays this information onto areas such as the lateral hypothalamus and the ventral tegmental area to modulate behavioral responses appropriate to particular environmental stimuli (Sheehan et al., 2004).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Sheehan et al., 2004 source

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Interpretationreasoning

    The context-specific effects of V1aR antagonist, AVP, OTR antagonist, and OXT treatments on social play could have been mediated by changes in the activation of motivational systems in the brain.

    “Hence, the context-specific effects of V1aR antagonist, AVP, OTR antagonist, and OXT treatments on social play could have been mediated by changes in the activation of motivational systems in the brain.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    These findings may be informative to humans, such that AVP- and/or OXT-based treatments of social deficits may have sex- and social context-dependent effects.

    “These findings may be informative to humans, such that AVP- and/or OXT-based treatments of social deficits may have sex- and social context-dependent effects.”
    Quote in the paperNot a substantial claim
31 of 31

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?

  • Blocking oxytocin reduces social play in juvenile rats, but only for females and only in certain contexts.

    “blocking oxytocin is known to reduce social play in juvenile rats but only for females and only in certain contexts (Bredewold et al., 2014).”

    From The evolved nest, oxytocin functioning, and prosocial development (2023) · cites this paper as Bredewold et al., 2014

    The Results (Modulation of social play behavior by OXT) state that oxytocin receptor antagonist treatment did not alter social play behavior. It was oxytocin treatment, not blockade, that reduced social play in females in the home cage. (LLM, conf=0.90)

    Checked by a reasoning model — may be wrong.

    Experimental — accuracy not yet measured

  • Of the AVP, glutamate, and GABA systems in the LS, AVP and glutamate regulate social play behavior in sex-specific ways.

    “Of these three systems, AVP and glutamate regulated social play behavior in sex-specific ways.”

    From Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum (2025) · cites this paper as Bredewold et al., 2014

    The Discussion conclusion (page not provided) states that AVP and OXT in the lateral septum regulate social play in juvenile rats in sex-specific, context-dependent ways. It supports the AVP portion, but does not support attributing a sex-specific glutamate effect to this paper; the other system it identifies is oxytocin, not glutamate. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • AVP, glutamate, and GABA systems in the LS each modulate social play behavior in both male and female juvenile rats.

    “We previously showed that arginine-vasopressin (AVP), glutamate, and GABA systems in the LS each modulate social play behavior in both male and female juvenile rats (Veenema et al., 2013, Bredewold et al., 2014, 2015).”

    From Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum (2025) · cites this paper as Bredewold et al., 2014

    The Results (Modulation of social play behavior by AVP) report that manipulating the lateral-septal AVP system changed social play in male and female juvenile rats, with effects dependent on sex and context. This paper examines AVP and oxytocin, not whether glutamate or GABA systems in the lateral septum modulate social play; those parts of the sentence are not supported by this source. Page numbers are unavailable in our copy. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • Administration of a V1aR antagonist into the LS increases social play levels in males and decreases it in females.

    “In detail, administration of the AVP V1a receptor (V1aR) antagonist into the LS increased social play levels in males and decreased it in females (Veenema et al., 2013, Bredewold et al., 2014) while administration of glutamate receptor antagonists into the LS decreased social play levels in females, while no changes in social play levels were seen in males (Bredewold et al., 2015).”

    From Vasopressin regulates social play behavior in sex-specific ways through glutamate modulation in the lateral septum (2025) · cites this paper as Bredewold et al., 2014

    The Results (Modulation of social play behavior by AVP, Treatment effects) report that V1aR antagonist treatment increased social play in males and decreased it in females in the home cage. The citing sentence omits that condition: the Discussion (context-specific effects) says these effects were absent in a novel cage. (LLM, conf=0.89)

    Experimental — accuracy not yet measured

  • The play-modulating effects of V1a receptor antagonism depend on social context and likely cannot be attributed to any effects on social recognition.

    “The play-modulating effects of V1a receptor antagonism depends on social context and likely cannot be attributed to any effects on social recognition (Bredewold et al., 2014), demonstrating the specificity of this node in the play circuit in light of the profound role for vasopressin in social behavior and social memory in adults (Albers, 2012).”

    From Developmental origins of sex differences in the neural circuitry of play (2020) · cites this paper as Bredewold et al., 2014

    The Discussion (context-specific effects; page unavailable) says V1aR blockade affected social play in the home cage but not in a novel cage. The paper does not establish that effects on social recognition are unlikely to explain this difference; its discussion of social recognition concerns other treatments or earlier studies. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

Statistics recomputed

Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.

  • ConsistentF(2, 104) = 3.96reported p < .05 · recomputed p = .022

    “F(2, 104) = 3.96, p < .05”

  • ConsistentF(2, 104) = 3.46reported p < .05 · recomputed p = .035

    “F(2, 104) = 3.46, p < .05”

  • ConsistentF(2, 104) = 6.86reported p < .005 · recomputed p = .002

    “F(2, 104) = 6.86, p < .005”

  • ConsistentF(2, 104) = 14.44reported p < .001 · recomputed p < .001

    “F(2, 104) = 14.44, p < .001”

  • ConsistentF(2, 104) = 8.96reported p < .005 · recomputed p < .001

    “F(2, 104) = 8.96, p < .005”

  • ConsistentF(1, 104) = 4.18reported p < .05 · recomputed p = .043

    “F(1, 104) = 4.18, p < .05”

  • ConsistentF(2, 53) = 15.3reported p < .001 · recomputed p < .001

    “F(2, 53) = 15.3, p < .001”

  • ConsistentF(2, 113) = 4.12reported p < .05 · recomputed p = .019

    “F(2, 113) = 4.12, p < .05”

  • ConsistentF(2, 113) = 3.64reported p < .05 · recomputed p = .029

    “F(2, 113) = 3.64, p < .05”

  • ConsistentF(1, 113) = 25.2reported p < .001 · recomputed p < .001

    “F(1, 113) = 25.2, p < .001”

  • ConsistentF(1, 113) = 55.3reported p < .001 · recomputed p < .001

    “F(1, 113) = 55.3, p < .001”

  • ConsistentF(1, 113) = 3.93reported p = .05 · recomputed p = .050

    “F(1, 113) = 3.93, p = .050”

  • ConsistentF(2, 62) = 5.01reported p < .05 · recomputed p = .010

    “F(2, 62) = 5.01, p < .05”

  • ConsistentF(2, 62) = 3.15reported p = .05 · recomputed p = .050

    “F(2, 62) = 3.15, p = .050”

  • ConsistentF(2, 51) = 3.41reported p < .05 · recomputed p = .041

    “F(2, 51) = 3.41, p < .05”

  • ConsistentF(2, 51) = 7.39reported p < .05 · recomputed p = .002

    “F(2, 51) = 7.39, p < .05”

16 of 16

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.

  • Sex effect has the wrong numerator degrees of freedom

    Minor

    Table 1 reports a numerator degree of freedom of 2 for a sex effect, but the study has only male and female groups. A sex effect with two groups has 1 numerator degree of freedom.

1 of 1

Cites

Flagged first, then by citations

Research works printed but not linked: 4

  1. Bekoff, 1998, Animal Play: Evolutionary, Comparative, and Ecological Perspectives, 10.1017/CBO9780511608575 · DOI
  2. Dumais, 2013b, Sex differences in oxytocin receptor binding in the bed nucleus of the stria terminalis and amygdala: Implications for differential expression and regulation of social behavior, Soc. Neurosci. Abstr
  3. Paxinos, 1998, The Rat Brain in Stereotaxic Coordinates
  4. Sigman, 1999, Continuity and change in the social competence of children with autism, Down syndrome, and developmental delays, Monogr. Soc. Res. Child. Dev, 64, 1, 10.1111/1540-5834.00002 · DOI

Cited by

Sorted by citations

Authors
Bredewold, R., Smith, C. J. W., Dumais, K. M., & Veenema, A. H.
Venue
Frontiers in Behavioral Neuroscience
Publisher
Frontiers Media SA
Published
2014-06-16
Volume
8
Pages
216-216
ISSN
1662-5153 (ISSN-L)
DOI
10.3389/fnbeh.2014.00216
PMC
PMC4058593
OpenAlex
W2166045656
Semantic Scholar
70c7a55f17f7a56688fd07a880c88b18c371daa7
Cited by
157
References
79
Citations by year
2026: 8 · 2025: 11 · 2024: 10 · 2023: 13 · 2022: 10 · 2021: 14 · 2020: 11 · 2019: 11 · 2018: 24 · 2017: 16 · 2016: 15 · 2015: 14
FWCI
21.52
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Behavioral Neuroscience (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (1253386)
  • Boston College
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
vasopressin, oxytocin, social play, young rats, lateral septum, V1a receptor, oxytocin receptor, sex differences, social environment, anxiety-like behavior, neuropeptides

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.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

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

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

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