CoChat
Sign Up
Cited by 74Neuroendocrine regulation and behaviorNeuropeptides and Animal PhysiologyOlfactory and Sensory Function Studies

Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network

Open access
DiBenedictis, Brett T., Nussbaum, Elizabeth R., Cheung, Harry K., Veenema, Alexa H.·2017·Journal of Comparative Neurology
DOI 10.1002/cne.24216PMC PMC6066795
Open this paper in CoChat — free account

Abstract

The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the "social behavior neural network" (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN. However, a thorough characterization of AVP and OT-immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats. We therefore quantified AVP- and OT-ir fibers and cell bodies in 22 subregions of the forebrain SBNN in juvenile and adult, male and female rats. We found numerous age (16 subregions) and sex (10 subregions) differences in AVP-ir fiber fractional areas, and AVP-ir cell body numbers, which were mainly observed in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit. In contrast to AVP, we observed no age or sex differences in OT-ir fiber fractional areas or cell bodies in any of the 22 subregions of the forebrain SBNN. Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic, which likely has significant functional consequences for the regulation of social behavior.

AI snapshot

Written from the paper’s full text.

TL;DR

Quantitative mapping in juvenile and adult, male and female rats found widespread age and sex differences in vasopressin (AVP) immunoreactivity across the forebrain social behavior neural network (SBNN), especially in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit, but no age or sex differences in oxytocin (OT) immunoreactivity. The authors conclude that AVP innervation of the forebrain SBNN undergoes developmental change and is highly sexually dimorphic, unlike the relatively static OT pattern.

Key findings

  • AVP-ir fiber fractional area showed age differences in 16 of 22 SBNN subregions and sex differences in 10 of 22 subregions in the abstract (the Results section reports sex differences in 12 of 22); most were in the MeA/BNST→LS circuit, with adults generally higher than juveniles and males generally higher than females.
  • Adult males had significantly more AVP-ir cell bodies in the pBNST and MeP than juvenile males and adult females; adult females had significantly more AVP-ir cell bodies in these regions than juvenile females.
  • The anterior hypothalamus (AHA) was the only forebrain SBNN region where AVP-ir was higher in juvenile males than adult males.
  • No age or sex differences were found in OT-ir fiber fractional areas in any of the 22 SBNN regions or in OT-ir cell body numbers in the aBNST/MPOA.

Methods

  • Juvenile (36-day-old) and adult (70-day-old) male and female Wistar rats (n = 7 per group) were perfused, and coronal sections were immunolabeled for AVP or OT using monoclonal antibodies PS41 and PS38.
  • AVP- and OT-ir fiber fractional areas were quantified in 22 forebrain SBNN subregions using ImageJ thresholding of 500 × 500 μm² images from three nonoverlapping sections per region; cell bodies were counted in the pBNST and MeP for AVP and in the aBNST/MPOA for OT, with Abercrombie correction.
  • Two-factor age × sex ANOVAs were used, with false discovery rate correction for fiber fractional area comparisons and Bonferroni post hoc tests for significant main effects.

Limitations

  • The paper states that fiber fractional area is not equivalent to true fiber density: it can reflect both fiber density and fiber caliber/peptide content, and true density would require stereological systematic-random sampling.
  • The paper states that no quantitative comparisons between AVP-ir and OT-ir fibers were made because OT-ir fibers appeared thicker than AVP-ir fibers in most regions.
  • The paper states that estrous cycle phase was not controlled in adult females, though variability in females was not greater than in males; females were sexually naïve, so it is unclear whether findings extend to lactating or pregnant females. Evident from the text: the study is correlational, uses only Wistar rats at two ages, and does not directly test behavioral consequences of the observed immunoreactivity differences.

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

Integrity signals

Registry

Crossref · 10.1002/cne.24216

Cites

104 of 104 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

18 of 71 cited sources checked · 11 supported · 1 flagged · accuracy not yet measured

  • Premisecitation

    Extracellular OT release in the pBNST was higher in adult male rats compared to adult female rats when exposed to a juvenile conspecific.

    “extracellular OT release in the pBNST was higher in adult male rats compared to adult female rats when exposed to a juvenile conspecific (Dumais et al., 2016)”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Dumais et al., 2016 source

      Section 2.b (Oxytocin; page unavailable) says that potential sex differences in brain OT release remain unclear because rat studies of region-specific release examined one sex only. Section 3.b reports higher oxytocin *receptor binding* in the posterior BNST of male rats, not higher extracellular OT release during exposure to a juvenile conspecific. (LLM, conf=0.86)

      Checked by a reasoning model — may be wrong.

      Experimental — accuracy not yet measured
  • Premisecitation

    AVP signaling in the LS regulates social play behavior in juvenile rats.

    “Moreover, AVP signaling in the LS regulates social play behavior in juvenile rats (Bredewold et al., 2014; Veenema et al., 2013).”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Bredewold et al., 2014 source
    • cites Veenema et al., 2013 source
  • Premisecitation

    Copulation with a female augments Fos expression in AVP-ir neurons in the MeP and BNST of adult male rats and mice.

    “In line with this, copulation with a female augments Fos expression in AVP-ir neurons in the MeP and BNST of adult male rats (Hari Dass & Vyas, 2014) and mice (Ho et al., 2010).”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hari Dass & Vyas, 2014 source

      Table 1 in Results and discussion shows a higher percentage of Fos-positive AVP-ir neurons in the MePD after copulation in male rats. The paper does not report that finding for the rat BNST; its discussion mentions BNST activation during copulation in mice, which the citing sentence attributes separately to Ho et al. (2010). (LLM, conf=0.88)

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

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

  • Premisecitation

    The MPOA contains oxytocin receptors in both sexes and at both juvenile and adult ages.

    “the MPOA contains oxytocin receptors in both sexes and at both juvenile and adult ages (Smith et al., 2017)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Smith et al., 2017 source
  • Premisecitation

    The MPOA is one of a few regions that show abundant AVP fibers but virtually no V1AR.

    “the MPOA is one of a few regions that show abundant AVP fibers, but virtually no V1AR (Smith et al., 2017)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Smith et al., 2017 source

      The Methods table lists OTR binding in the MPOA, but gives no MPOA V1aR measurement. The Introduction describes AVP fiber projections broadly, not abundant fibers in the MPOA. Searches for MPOA, AVP fibers, and absent V1aR found no passage establishing the claimed combination. (LLM, conf=0.72)

      Experimental — accuracy not yet measured
  • May combine two claims. 23
  • Classified as probably not a substantial claim. 26

  • May combine two claims.

    Premisecitation

    LS-V1AR blockade did not impair social recognition in juvenile rats, but rather induced a preference to investigate familiar over novel conspecifics.

    “Surprisingly, LS-V1AR blockade did not impair social recognition in juvenile rats, but rather induced a preference to investigate familiar over novel conspecifics (Veenema et al., 2012).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Veenema et al., 2012 source

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

    Premisecitation

    Male rats castrated as adults show reduced AVP-ir in the MeP/pBNST→LS circuit as well as reduced levels of intermale aggression.

    “A potential role of AVP in male aggression is largely based on the observation that male rats castrated as adults show reduced AVP-ir in the MeP/pBNST→LS circuit as well as reduced levels of intermale aggression (Koolhaas, Moor, Hiemstra, & Bohus, 1991; Miller et al., 1992; Szot & Dorsa, 1993; van Leeuwen et al., 1985).”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Koolhaas et al., 1991

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

    • cites Miller et al., 1992 source

      The paper reports that castration of adult male rats reduces vasopressin immunoreactivity in BNST neurons; its introduction also describes a postcastration loss of immunoreactive fibers in the septum, and the Discussion notes a similar, unquantified decline in the medial amygdala (page numbers unavailable). It does not report reduced intermale aggression, so that part of the claim is unsupported by this source. (LLM, conf=0.89)

      Experimental — accuracy not yet measured
    • cites van Leeuwen et al., 1985 source

  • May combine two claims.

    Premisecitation

    In adult male and female rats, administration of AVP in the lateral septum prolonged social recognition, while administration of V1AR antagonists in the lateral septum impaired social recognition.

    “administration of AVP in the LS prolonged, while administration of V1AR antagonists in the LS impaired social recognition similarly in adult male and female rats (Veenema et al., 2012)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Veenema et al., 2012 source

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

    Premisecitation

    AVP mRNA expression in BNST neurons increased following mating in male, but not female, prairie voles.

    “For example, AVP mRNA expression in BNST neurons increased following mating in male, but not female, prairie voles (Wang, Ferris, & De Vries, 1994).”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites Wang et al., 1994 source

      The available article text reports changes in vasopressin-immunoreactive fibers in the lateral septum after males were paired with females, not AVP mRNA expression in BNST neurons. Searches for BNST mRNA and a male–female mating comparison found no passage establishing the claimed increase or sex difference; the available copy links to a PDF but does not include its body text. (LLM, conf=0.70)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    AVP-ir fibers, and to a lesser extent OT-ir fibers and their receptors, have been observed in several forebrain constituents of the SBNN in rodents.

    “AVP-ir fibers, and, to a lesser extent, OT-ir fibers and their receptors have been observed in several forebrain constituents of the “social behavior neural network” (SBNN) in rodents”
    Quote in the paperSubstantial claim1 of 3 sources checked
    • cites Bakker et al., 2006 source
    • cites Rood et al., 2013 source
    • cites Smith et al., 2017 source

      The Introduction (page unavailable) says OT- and AVP-producing nuclei project fibers to many brain regions and that both receptors are widely distributed. The Discussion (page unavailable) identifies several receptor-bearing regions as nodes of the social behavior network. However, the paper does not establish that OT-immunoreactive fibers or their receptors occur there to a lesser extent than AVP-immunoreactive fibers; its measurements concern receptor binding, not that comparison of fibers. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

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

    Premisecitation

    In rats, males have more AVP-expressing neurons in the BNST and MeA and have a higher density of AVP-immunoreactive fibers in the LS and lateral habenular nucleus compared to females.

    “In rats, males have more AVP-expressing neurons in the BNST and MeA (Szot & Dorsa, 1993; van Leeuwen, Caffe, & De Vries, 1985) and have a higher density of AVP-immunoreactive (AVP-ir) fibers in the lateral septum (LS) and lateral habenular nucleus (De Vries, Buijs, & Swaab, 1981) compared to females.”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Szot & Dorsa, 1993

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

    • cites van Leeuwen et al., 1985 source
    • cites De Vries et al., 1981 source

  • May combine two claims.

    Premisecitation

    Blockade of the AVP V1A receptor in the LS impaired social recognition in adult rats, while AVP infusions into the LS improved it.

    “Here, blockade of the AVP V1A receptor (V1AR) in the LS impaired social recognition in adult rats, while AVP infusions into the LS improved it (Dantzer et al., 1988; Engelmann & Landgraf, 1994; Everts & Koolhaas, 1997; Lukas, Toth, Veenema, & Neumann, 2013; Veenema et al., 2012).”
    Quote in the paperNot a substantial claim1 of 3 sources checked
    • cites Dantzer et al., 1988 source
    • cites Engelmann & Landgraf, 1994 source
    • cites Veenema et al., 2012 source

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

    Premisecitation

    Adult rats expressed higher OTR binding density than juvenile rats in the pBNST, MePD, MPOA, and VMH; juveniles had higher OTR binding in the ventral LS; and males had higher OTR binding in these regions than females.

    “adult rats expressed higher OTR binding density compared to juvenile rats in the pBNST, MePD, MPOA, and VMH, while juveniles had higher OTR binding in the ventral portion of the LS and males had higher levels of OTR binding in these regions compared to females (Smith et al., 2017)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Smith et al., 2017 source

      The Results section on age differences reports higher OTR binding in adults in the pBNST, MePD, MPOA, and VMH, and higher binding in juveniles in the ventral lateral septum (page unavailable). The sex-differences Results report higher binding in males in the pBNST, MePD, and VMH, but do not list the MPOA or ventral lateral septum; the Discussion does describe higher binding in males in the MPOA. Thus, the claim that males had higher binding in all the named regions is not supported for the ventral lateral septum. (LLM, conf=0.84)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Robust age and sex differences were found for the oxytocin receptor (OTR) across multiple nodes of the rat SBNN.

    “robust age and sex differences were found for the OTR across multiple nodes of the rat SBNN (Smith et al., 2017)”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites Smith et al., 2017 source

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

    Premisecitation

    AVP, OT, and their homologs regulate social behavior across vertebrate taxa.

    “AVP, OT, and their homologs regulate social behavior across vertebrate taxa (for review, see Goodson 2008; Kelly & Ophir 2015)”
    Quote in the paperNot a substantial claim2 of 2 sources checked
    • cites Goodson 2008 source
    • cites Kelly & Ophir 2015 source

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

    Premisecitation

    In adult female rats, MPOA lesions facilitated the display of sexual behavior.

    “MPOA lesions facilitated the display of sexual behavior in adult female rats (Hoshina, Takeo, Nakano, Sato, & Sakuma, 1994; Powers & Valenstein, 1972)”
    Quote in the paperNot a substantial claim1 of 2 sources checked
    • cites Hoshina, Takeo, Nakano, Sato, & Sakuma, 1994 source
    • cites Powers & Valenstein, 1972 source

  • May combine two claims.

    Findingown data

    Ten of 22 SBNN subregions showed significant sex differences in AVP-ir fiber fractional area, higher in males.

    “10 of 22 SBNN subregions showing significant sex differences (higher in males).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adult males showed a greater AVP-ir fiber fractional area compared to adult females in 5 LS subregions (mLSD, mLSI, mLSV, cLSI, cLSV), 2 BNST subregions (STMAM, STLI), MPOA, and all four MeA subregions (MeAD, MeAV, MePD, MePV).

    “Specifically, adult males showed a greater fractional area occupied by AVP-ir fibers compared to adult females in 5 subregions of the LS (mLSD, mLSI, mLSV, cLSI, and cLSV), 2 subregions of the BNST (STMAM, STLI), the MPOA, and all four subregions of the MeA (MeAD, MeAV, MePD, and MePV).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Overall, high density of AVP-ir fibers occupying a large fractional area in key SBNN nodes, including LS, BNST, and MeA in adult males, whereas OT-ir in these regions was relatively sparse.

    “Overall, we observed a high density of AVP-ir fibers occupying a large fractional area in key SBNN nodes, including the LS, BNST, and MeA in adult males (Figure 6a–c), whereas OT-ir in these regions was relatively sparse (Figure 6a–c′).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the medial preoptic area (MPOA), AVP fiber fractional area showed sex differences already at the juvenile age, with males having higher density than females, and this effect persisted into adulthood.

    “Sex differences in AVP fiber fractional area in the MPOA were already apparent at the juvenile age, with males having a higher density of AVP fibers than females, and this effect persisted into adulthood.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    In the anterior portion of the anterior hypothalamus (AHA), AVP-ir was higher in juvenile males than in adult males, and this was the only region in the forebrain SBNN where this age difference was observed.

    “The anterior portion of the AH (AHA) was the only region in the fore-brain SBNN in which AVP-ir was higher in juvenile males than in adult males.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There are many age (juveniles vs. adults) and sex differences in AVP-ir, but not OT-ir, throughout the forebrain SBNN in rats, most notably in the LS, BNST, and MeA (age and sex), as well as the AH (age only) and MPOA (sex only).

    “we showed for the first time that there are many age (juveniles vs. adults) and sex differences in AVP-ir (but not OT-ir) throughout the forebrain SBNN, most notably the LS, BNST, and MeA (age and sex), as well as the AH (age only) and MPOA (sex only) in rats.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Unlike OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes and is highly sexually dimorphic.

    “Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationcitation

    Sex differences in circulating gonadal hormone levels may be necessary, but are less likely to be sufficient to induce sex-specific AVP expression in this circuit.

    “However, sex differences in circulating gonadal hormone levels may be necessary, but are less likely to be sufficient to induce sex-specific AVP expression in this circuit.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites De Vries & al-Shamma, 1990 source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    The false discovery rate (FDR) procedure was used to correct for multiple comparisons.

    “The false discovery rate (FDR) procedure was used to correct for multiple comparisons based on main effects, and were calculated separately for AVP and OT fiber fractional area measurements (AVP: α <0.024; OT: α <0.004; Benjamini & Hochberg, 1995).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Benjamini & Hochberg, 1995 source

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

    Premisecitation

    In adult male rats, lesions of the MPOA reduced sexual behavior, while electrical stimulation of the MPOA facilitated sexual behavior.

    “In adult male rats, lesions of the MPOA reduced, while electrical stimulation of the MPOA facilitated sexual behavior (Arendash & Gorski, 1983; Malsbury, 1971).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Arendash & Gorski, 1983 source
    • cites Malsbury, 1971 source

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    An Abercrombie correction was applied to all cell counts to correct for overcounting in profile sections.

    “An Abercrombie (1946) correction was applied to all cell counts in order to correct for overcounting in profile sections (see Guillery, 2002).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Abercrombie, 1946 source
    • cites Guillery, 2002 source

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

    Premisecitation

    AVP signaling in the anterior hypothalamus facilitates intermale aggression in diverse adult rodent species.

    “AVP signaling in the AH facilitates intermale aggression in diverse adult rodent species (Albers et al., 2006; Caldwell & Albers, 2004; Cooper, Karom, Huhman, & Albers, 2005; Gobrogge, Liu, Young, & Wang, 2009; Ferris et al., 1997; Potegal & Ferris, 1989)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Albers et al., 2006 source
    • cites Caldwell & Albers, 2004 source
    • cites Cooper, Karom, Huhman, & Albers, 2005 source

  • Classified as probably not a substantial claim.

    Premisecitation

    Extracellular AVP release in the LS decreased during intermale aggression in rats showing high levels of aggression.

    “extracellular AVP release in the LS decreased during intermale aggression in rats showing high levels of aggression (Beiderbeck, Neumann, & Veenema, 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Beiderbeck et al., 2007 source

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

    Premisecitation

    Extracellular AVP release in the LS correlated positively with intermale aggression in testes intact rats.

    “extracellular AVP release in the LS correlated positively with intermale aggression in testes intact rats (Veenema et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Veenema et al., 2010 source

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

    Premisecitation

    Administration of AVP into the LS facilitated intermale aggression in castrated rats.

    “For example, administration of AVP into the LS facilitated inter-male aggression in castrated rats (Koolhaas et al., 1991)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Koolhaas et al., 1991

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

  • May combine two claims.

    Interpretationcitation

    The role of AVP in the MeP/pBNST→LS circuit largely depends on individual differences in innate levels of intermale aggression, and higher AVP-ir may not directly translate to higher levels of aggression.

    “Taken together, these studies suggest that the role of AVP in this circuit largely depends on individual differences in innate levels of intermale aggression, and that higher AVP-ir may not directly translate to higher levels of aggression.”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Compaan et al., 1993 source
    • cites Everts & Koolhaas, 1997 source
    • cites Beiderbeck et al., 2007 source

  • May combine two claims.

    Premisecitation

    Gonadectomized adult male and female rats exposed to similar levels of testosterone still differ, with adult males having higher AVP expression than adult females.

    “For example, gona-dectomized adult male and female rats exposed to similar levels of testosterone still differ, with adult males having higher AVP expression than adult females (De Vries & al-Shamma, 1990).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites De Vries & al-Shamma, 1990 source

  • Classified as probably not a substantial claim.

    Premisecitation

    The specific pattern of activity across the interconnected SBNN is thought to underlie the expression of a particular social behavior.

    “In this model, the specific pattern of activity across this interconnected network is thought to underlie the expression of a particular social behavior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Newman, 1999 source

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

    Study design and conductown data

    The experimenter analyzing slides was blind to treatment groups.

    “Slides were coded prior to image acquisition and, in all cases, analyzed by an experimenter blind to treatment groups.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    Male rats showed an augmented Fos response in the MPOA following copulation with an estrous female rat.

    “male rats showed an augmented Fos response in the MPOA following copulation with an estrous female rat (Baum & Everitt, 1992)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Baum & Everitt, 1992 source

  • May combine two claims.

    Premisecitation

    Intracerebroventricular administration of AVP decreases hop-dart proceptive behaviors as well as lordosis responses in female rats, an effect rescued by central infusion of a V1AR antagonist.

    “Interestingly, intracerebroventricular administration of AVP decreases hop-dart proceptive behaviors as well as lordosis responses in female rats, an effect that is rescued by central infusion of a V1AR antagonist (Pedersen & Boccia, 2006).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pedersen & Boccia, 2006 source

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

    Premisecitation

    AVP and OT signaling within the SBNN differentially regulate diverse social behaviors, depending on the age and/or sex of the animal.

    “Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    All regions of the forebrain SBNN are interconnected, express gonadal hormone receptors, and have been individually identified as important sites of regulation or activation of social behaviors.

    “All of these regions are interconnected, express gonadal hormone receptors, and have been individually identified as important sites of regulation or activation of a multitude of social behaviors, from pair bonding, to sexual and maternal behaviors (Newman, 1999).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Newman, 1999 source

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

    Premisecitation

    The OT system undergoes dramatic changes during pregnancy and lactation to facilitate maternal behaviors.

    “the OT system undergoes dramatic changes during pregnancy and lactation to facilitate maternal behaviors (Jirikowski, Caldwell, Pilgrim, Stumpf, & Pendersen, 1989; Meddle, Bishop, Gkoumassi, van Leeuwen, & Douglas, 2007; Pedersen, Ascher, Monroe, & Prange, 1982; Theodosis, Montagnese, Rodriguez, Vincent, & Poulain, 1986)”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Jirikowski et al., 1989 source
    • cites Meddle et al., 2007 source
    • cites Pedersen et al., 1982 source

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

    Premisecitation

    Pup exposure-induced maternal behavior in juvenile female rats relies on the MPOA.

    “pup exposure-induced maternal behavior in juvenile female rats relies on the MPOA (Kalinichev, Rosenblatt, & Morrell, 2000)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kalinichev, Rosenblatt, & Morrell, 2000

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

  • May combine two claims.

    Interpretationcitation

    Despite lower levels of AVP-ir in the network, AVP signaling is crucial for the proper display of social behaviors in juveniles (social play, social recognition) and adult females (social recognition, sexual behavior).

    “despite having lower levels of AVP-ir in this network, AVP signaling is nevertheless crucial for the proper display of social behaviors in juveniles (social play, social recognition) and adult females (social recognition, sexual behavior)”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    There may be age and sex differences in the mechanisms regulating OT release, particularly in response to social stimuli.

    “Additionally, there may be age and sex differences in the mechanisms regulating OT release, particularly in response to social stimuli.”
    Quote in the paperNot a substantial claim

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

    Premisecitation

    MPOA lesions disrupt the onset and the maintenance of maternal behavior.

    “MPOA lesions also disrupt the onset and the maintenance of maternal behavior (Numan, 1974; Numan, Rosenblatt, & Komisaruk, 1977)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Numan, 1974 source
    • cites Numan, Rosenblatt, & Komisaruk, 1977 source

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

    Premisecitation

    The display of maternal behavior in lactating rats is associated with increased extracellular AVP release in the MPOA.

    “the display of maternal behavior in lactating rats is associated with increased extra-cellular AVP release in the MPOA (Bosch et al., 2010)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Bosch et al., 2010 source

  • May combine two claims.

    Interpretationcitation

    The function of AVP may differ depending on age (juvenile versus adult social recognition) or sex (male versus female sexual behavior).

    “the function of AVP may differ depending on age (juvenile versus adult social recognition) or sex (male versus female sexual behavior).”
    Quote in the paperSubstantial claim

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

    Interpretationcitation

    Activation of the MPOA inhibits pathways mediating female sexual behaviors, but activates pathways mediating maternal behaviors.

    “suggesting that activation of the MPOA inhibits pathways mediating female sexual behaviors, but activates pathways mediating maternal behaviors.”
    Quote in the paperNot a substantial claim
42 of 42

  • The paper relies on this without support.

    A thorough characterization of AVP and OT-immunoreactive fibers and cell bodies across age and sex within the SBNN has been lacking in rats.

    “However, a thorough characterization of AVP and OT-immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats.”
    “However, a thorough, quantitative analysis of age and sex differences in AVP and OT-ir in most regions of the SBNN is lacking in rats.”

  • The paper relies on this without support.

    A direct comparison of adult and juvenile AVP and OT synthesis and fiber projections in regions implicated in social behavior has been lacking.

    “yet despite this critical period in social development, a direct comparison of adult and juvenile AVP and OT synthesis and fiber projections in regions implicated in social behavior has been lacking.”
2 of 2

Claims other papers make about this one

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

  • Oxytocin neurons have been reported in the extended medial amygdala (bed nucleus of the stria terminalis and medial amygdala proper) in rats, California mice, and marmosets.

    “Oxytocin OXT neurons have been reported in the extended medial amygdala (eg, the BNST and medial amygdala proper [MeA]) in rats (63), California mice (64), and marmosets (65).”

    From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [63]

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.

  • AVP-ir sex-difference count is reported as both 12 and 10 subregions

    Minor

    The Results report sex differences in 12 of 22 subregions, while the Discussion reports 10 of 22. The Results' listed subregions also total 12.

1 of 1

Cites

Flagged first, then by citations

1 of the 105 references couldn’t be matched to a known paper.

Research works printed but not linked: 3

  1. Baum M. J., 2009, Opposite‐sex volatile urinary odors detected by the main and processed via the accessory olfactory system contribute to mate recognition in mice, Chemical Senses, 34, A4
  2. Koolhaas J. M., 1991, The testosterone‐dependent vasopressinergic neurons in the medial amygdala and lateral septum: Involvement in social behaviors of male rats, 213
  3. Paxinos G., 2007, The rat brain atlas in stereotaxic coordinates

Cited by

Sorted by citations

Related

Authors
DiBenedictis, B. T., Nussbaum, E. R., Cheung, H. K., & Veenema, A. H.
Affiliations
Boston College (US)
Corresponding author
DiBenedictis, Brett T.
ORCID
Venue
Journal of Comparative Neurology
Publisher
Wiley
Published
2017-05-08
Volume
525
Issue
11
Pages
2549-2570
ISSN
  • 0021-9967 (ISSN-L)
  • 1096-9861
DOI
10.1002/cne.24216
PMC
PMC6066795
OpenAlex
W2600095846
Semantic Scholar
2b3d9a73ccf32877717a411b635b140bf4227af5
Cited by
74
References
105
Citations by year
2026: 4 · 2025: 5 · 2024: 11 · 2023: 4 · 2022: 7 · 2021: 9 · 2020: 8 · 2019: 9 · 2018: 11 · 2017: 5
FWCI
12.40
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The Journal of Comparative Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (submittedVersion)
  • PubMed Central (submittedVersion)
Funders
National Institutes of Health (R15MH102807)
Topics
  • Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
  • Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
Keywords
vasopressin, oxytocin, age differences, sex differences, neuropeptide immunoreactivity, medial amygdala, bed nucleus of the stria terminalis, lateral septum, developmental changes, social behavior regulation, rats
MeSH terms
Age Factors, Animals, Brain Mapping, Female, Male, Nerve Net, Oxytocin, Sex Characteristics, Social Behavior, Vasopressins, Prosencephalon, Rats, Wistar, Rats

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 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

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 ›

Are you an author, or do you see a problem with this page? Request a review