Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles
Open accessAbstract
Oxytocin (OT) is a deeply conserved nonapeptide that acts both peripherally and centrally to modulate reproductive physiology and sociosexual behavior across divergent taxa, including humans. In vertebrates, the distribution of the oxytocin receptor (OTR) in the brain is variable within and across species, and OTR signaling is critical for a variety of species-typical social and reproductive behaviors, including affiliative and pair bonding behaviors in multiple socially monogamous lineages of fishes, birds, and mammals. Early work in prairie voles suggested that the endogenous OT system modulates mating-induced partner preference formation in females but not males; however, there is significant evidence that central OTRs may modulate pair bonding behavior in both sexes. In addition, it remains unclear how transient windows of central OTR signaling during sociosexual interaction modulate neural activity to produce enduring shifts in sociobehavioral phenotypes, including the formation of selective social bonds. Here we re-examine the role of the central OT system in partner preference formation in male prairie voles using a selective OTR antagonist delivered intracranially. We then use the same antagonist to examine how central OTRs modulate behavior and immediate early gene (Fos) expression, a metric of neuronal activation, in males during brief sociosexual interaction with a female. Our results suggest that, as in females, OTR signaling is critical for partner preference formation in males and enhances correlated activation across sensory and reward processing brain areas during sociosexual interaction. These results are consistent with the hypothesis that central OTR signaling facilitates social bond formation by coordinating activity across a pair bonding neural network.
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Written from the paper’s full text.
TL;DR
Central oxytocin receptor (OTR) blockade in male prairie voles prevents mating-induced partner preference formation and reduces mating bouts, while leaving Fos induction in individual forebrain nuclei largely unchanged. OTR signaling during sociosexual interaction instead appears to enhance correlated Fos activation across a hypothesized pair-bonding network.
Key findings
- ICV oxytocin receptor antagonist (OTA) blocked partner preference in male prairie voles: aCSF-treated males spent more time huddling with the partner than the stranger (n=16; p=0.0028), whereas OTA-treated males did not (n=16; p=0.95); stimulus × treatment interaction F1,60=6.208, p=0.016, d=1.20.
- OTA reduced mating frequency during a 30-min cohabitation: OTA-treated males had 2.49±0.62 mating bouts per 30 min versus 5.30±1.14 in aCSF-treated males (Poisson regression z=-4.30; p=2.35×10^-5).
- Mating, not OTA treatment, was associated with elevated Fos in the medial preoptic area (MPOA): mated males (n=20) had higher MPOA Fos than exposed non-mated males (n=11; p=0.0024; d=1.4), with no significant treatment effect.
- Among mated males, OTA did not significantly alter Fos in any individual PBN nucleus, but it disrupted correlated Fos expression across the network: first principal component explained 68.6% of variance in aCSF-mated males versus 35.3% in OTA-mated males, a 33.3% difference (permutation p=0.008).
Methods
- Adult male prairie voles (60–200 days) received unilateral ICV cannulation and microinjections of aCSF or a selective OTR antagonist (2.5 ng/μL in 2 μl) for two experiments.
- Experiment 1: after 48-h cohabitation with an estrogen-primed female, males underwent a 3-h partner preference test; final groups were n=16 aCSF and n=16 OTA after cannula-placement exclusions.
- Experiment 2: after a 30-min cohabitation, sociosexual behaviors were scored and Fos immunohistochemistry was quantified in the MPOA and 7 OTR-expressing PBN nuclei; analyses used ANOVA, t-tests, Poisson regression, PCA, and permutation testing.
Limitations
- Stated: correlated Fos patterns do not reveal specific neuronal phenotypes or dynamic electrophysiological network properties; small sample sizes, many pairwise comparisons, and brain-wide OTR blockade preclude conclusions about specific PBN nuclei; whole-nucleus resolution ignores heterogeneous cell populations; the behavioral paradigm included varied complex social interactions; and the study does not address how social context relates to central OTR effects.
- Evident from the text: the study is restricted to male prairie voles, so it cannot directly compare sexes; Fos covariance is correlational and cannot establish causal direction or real-time functional connectivity; and analyses of PBN Fos were restricted to mated subjects, limiting generalization to non-mating sociosexual interactions.
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Cites
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Claims the paper makes
0 of 38 cited sources checked · 0 supported · 0 flagged
- Findingown data
Among mated male prairie voles, oxytocin receptor antagonist versus artificial cerebrospinal fluid treatment has no detectable effect on analyzed sociosexual behaviors.
“among mated animals, OTA versus aCSF treatment had no detectable effect on any of the analyzed sociosexual behaviors.”
Quote in the paperNot a substantial claim - Findingown data
Central oxytocin receptor signaling during sociosexual interaction does not modulate Fos expression within any of the analyzed pair bonding network nuclei in male prairie voles.
“we restrict our analysis to nuclei within the PBN and find no evidence that central OTR signaling during sociosexual interaction modulates Fos expression within any of the analyzed brain nuclei.”
- Also stated in: § OTR signaling during sociosexual interaction and Fos expression in PBN nuclei · plain
“OTA did not significantly modulate Fos induction within any of the analyzed nuclei.”
Quote in the paperSubstantial claim - Also stated in: § OTR signaling during sociosexual interaction and Fos expression in PBN nuclei · plain
- Findingown data
Mating is associated with elevated Fos expression within the medial preoptic area in male prairie voles.
“a Student's t-test revealed significantly elevated Fos expression in subjects that mated (n=20) versus subjects that were exposed to a female but that did not mate (n=11; p=0.0024; Figure 2B; d=1.4)”
Quote in the paperNot a substantial claim - Findingown data
Sociosexual interaction and mating is associated with significant elevation in Fos expression across the pair bonding network in mated animals relative to unexposed controls.
“A one-way repeated measures ANOVA revealed a significant effect of sociosexual interaction and mating on Fos expression across the PBN between mated animals (pooled) and unexposed controls (F1,191=18.51; p=3.20×10-5; Eta-squared=0.07; Figure 4).”
Quote in the paperSubstantial claim - Findingown data
The 30-minute cohabitation paradigm is a useful tool for investigating sexual behavior and neural activity in male prairie voles.
“We first demonstrate that this paradigm is a useful tool for investigating sexual behavior and neural activity in male prairie voles by replicating findings from investigations in other rodents.”
Quote in the paperSubstantial claim
- Findingown data
Central oxytocin receptor signaling is critical for partner preference formation in male prairie voles.
“we revisit the role of OTR in partner preference formation in male prairie voles, and demonstrate conclusively using a highly selective OTR antagonist (OTA) that, as in females, central OTR signaling is critical for pair bonding in males.”
- Also stated in: § Effects of central OTA on male partner preference formation · plain
“male prairie voles spent significantly more time in social contact with their partner versus the stranger following ICV administration of aCSF (n=16; p=0.0028) but not OTA (n=16; p=0.95; Figure 1).”
Quote in the paperSubstantial claim - Also stated in: § Effects of central OTA on male partner preference formation · plain
- Findingown data
Central administration of an oxytocin receptor antagonist reduces intromission frequency during sociosexual interaction in male prairie voles.
“intromission frequency was reduced in OTA-treated (2.49±0.62 mating bouts per 30 minutes) relative to aCSF-treated (5.30±1.14 mating bouts per 30 minutes) subjects.”
Quote in the paperSubstantial claim - Findingown data
Artificial cerebrospinal fluid-treated male prairie voles spent significantly more time in social contact with their partner versus the stranger.
“male prairie voles spent significantly more time in social contact with their partner versus the stranger following ICV administration of aCSF (n=16; p=0.0028) but not OTA (n=16; p=0.95; Figure 1).”
Quote in the paperSubstantial claim - Findingown data
In aCSF-treated mated animals, the first principal component accounts for 68.6% of the variance in Fos expression across PBN nuclei.
“Consistent with the increase in correlated Fos expression across PBN nuclei in aCSF-treated mated animals (Figure 5b), PCA revealed that the first principal component accounts for 68.6% of the variance.”
Quote in the paperSubstantial claim - Findingown data
Permutation testing of the difference in variance explained by the first principal component between aCSF- and OTA-treated mated subjects resulted in a p-value of 0.008.
“This resulted in a p-value of 0.008, suggesting that OTA significantly disrupts the increase in correlated Fos expression across the PBN induced by sociosexual interaction and mating.”
Quote in the paperSubstantial claim - Findingown data
There was a significant stimulus by treatment interaction on duration of immobile social contact during the partner preference test.
“A two-way ANOVA revealed a significant main effect of stimulus (partner versus stranger; F1,60=5.77; p=0.019), and stimulus by treatment (aCSF versus OTA) interaction (F1,60=6.208; p=0.016; d=1.20), but not of treatment (F1,60=0.429; p=0.51) on duration of immobile social contact (e.g. huddling) during the partner preference test.”
Quote in the paperSubstantial claim - Findingown data
In OTA-treated mated animals, the first principal component accounts for 35.3% of the variance.
“In contrast, in OTA-treated mated animals, the first principal component accounts for 35.3% of the variance.”
Quote in the paperSubstantial claim - Findingown data
Oxytocin receptor antagonist-treated male prairie voles did not spend significantly more time in social contact with their partner versus the stranger.
“male prairie voles spent significantly more time in social contact with their partner versus the stranger following ICV administration of aCSF (n=16; p=0.0028) but not OTA (n=16; p=0.95; Figure 1).”
Quote in the paperSubstantial claim - Findingown data
Relative to aCSF-treated mated animals, OTA injected animals exhibit a weaker, less uniform pattern of correlated Fos expression across the network.
“In contrast, as seen in Figure 5c, relative to aCSF-treated mated animals, OTA injected animals exhibit a weaker, less uniform pattern of correlated FOS expression across the network.”
Quote in the paperSubstantial claim - Findingown data
The difference in variance explained by the first principal component between aCSF- and OTA-treated mated subjects is 33.3%.
“We then used permutation testing to test whether this difference (33.3%) in variance explained by the first principal component between aCSF- and OTA-treated mated subjects exceeds what would be expected by chance (see “Materials and Methods”).”
Quote in the paperSubstantial claim - Findingown data
Fos expression is significantly elevated in every analyzed pair bonding network region except the paraventricular hypothalamic nucleus in mated subjects relative to unexposed controls.
“Fos expression was significantly (p<0.007) elevated in every analyzed region, except the PVN (p=0.023), in mated subjects relative to unexposed controls.”
Quote in the paperNot a substantial claim - Findingown data
Relative to unexposed controls, sociosexual interaction and mating results in a strong and relatively uniform increase in correlated Fos expression across the network.
“Relative to unexposed controls, sociosexual interaction and mating results in a strong and relatively uniform increase in correlated Fos expression across the network (Figure 5b).”
Quote in the paperSubstantial claim - Findingown data
Under control conditions (no exposure to a female), Fos expression is weakly correlated across nodes, as measured by Pearson's correlation coefficients.
“As seen in Figure 5a, under control conditions (no exposure to a female) Fos expression is weakly correlated across nodes, as measured by Pearson's correlation coefficients.”
Quote in the paperSubstantial claim - Findingown data
OTA administration inhibited partner preference formation in mated male prairie voles (p=0.016).
“In contrast to the previous study, OTA administration inhibited partner preference formation in mated male prairie voles (p=0.016).”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Findingown data
Intromission during the 30-minute period of sociosexual interaction was associated with a significant, non-OT-dependent elevation in MPOA Fos expression (p=0.0024).
“Indeed, intromission during the 30-minute period of sociosexual interaction was associated with a significant, non-OT-dependent elevation in MPOA Fos expression (p=0.0024)”
Quote in the paperNot a substantial claim - Findingown data
No significant differences were observed in Fos expression within any brain region between OTA- and aCSF-mated animals.
“but no significant differences were observed in Fos expression within any brain region between OTA- and aCSF-mated animals.”
Quote in the paperSubstantial claim - Findingown data
Central OTR blockade reduced frequency of mating bouts (n=20) relative to aCSF-treatment (n=16) during sociosexual interaction with a female (p=2.35×10-5).
“Consistent with these data, central OTR blockade reduced frequency of mating bouts (n=20) relative to aCSF-treatment (n=16) during sociosexual interaction with a female (p=2.35×10-5)”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Findingown data
Sociosexual interaction and mating with a female was associated with significantly elevated Fos expression across the analyzed PBN nuclei (p=1.03×10-6).
“Sociosexual interaction and mating with a female was associated with significantly elevated Fos expression across the analyzed PBN nuclei (p=1.03×10-6)”
Quote in the paperSubstantial claim - Premisecitation
In male and female prairie voles, mating facilitates pair bonding.
“In male and female prairie voles, mating facilitates pair bonding.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Williams et al., 1992a
Not checked in the free run.
- Premisecitation
Blocking oxytocin receptors in the prefrontal cortex or nucleus accumbens prevents mating-induced partner preferences in female prairie voles.
“More specifically, blocking OTR in the prefrontal cortex (PFC) or nucleus accumbens (NA) prevents mating-induced partner preferences in females (Young et al., 2001).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Young et al., 2001 source
Not checked in the free run.
- Premisecitation
A single seminal paper failed to show that oxytocin receptor blockade inhibits mating-induced partner preferences in male prairie voles.
“a single seminal paper failed to show that OTR blockade inhibits mating induced partner preferences in males (Winslow and Insel, 1993).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Winslow and Insel, 1993 source
Not checked in the free run.
- Premisecitation
Central OT administration enhances partner preference formation in both female and male prairie voles.
“and central OT administration enhances partner preference formation in both females and males (Cho et al., 1999).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cho et al., 1999 source
Not checked in the free run.
- Interpretationown data
OTA significantly disrupts the increase in correlated Fos expression across the PBN induced by sociosexual interaction and mating.
“This resulted in a p-value of 0.008, suggesting that OTA significantly disrupts the increase in correlated Fos expression across the PBN induced by sociosexual interaction and mating.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Study design and conductown data
Among animals that mated, there were no observed differences in behavior (e.g. non-investigation, investigation, mounting, or intromission) between OTA- and aCSF-treated groups.
“It is important to note that among those animals that mated, there were no observed differences in behavior (e.g. non-investigation, investigation, mounting, or intromission) between OTA- and aCSF-treated groups.”
Quote in the paperSubstantial claim - Interpretationown data
The data are consistent with a broader interpretation that central OTR signaling during sociosexual interaction and mating promotes increased functional connectivity across the network as a whole.
“instead, the data are consistent with a broader interpretation that central OTR signaling during sociosexual interaction and mating promotes increased functional connectivity across the network as a whole.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Interpretationcitation
These data are consistent with previously outlined hypotheses that neuropeptide signaling can modulate adaptive forms of sociobehavioral plasticity in part by modulating patterns of functional connectivity across evolutionarily conserved neural networks, such as the social decision making network in vertebrates, during social and reproductive contexts that elicit OT and AVP release.
“Despite these limitations, these data are consistent with previously outlined hypotheses (Goodson and Kabelik, 2009) that neuropeptide signaling can modulate adaptive forms of sociobehavioral plasticity in part by modulating patterns of functional connectivity across evolutionarily conserved neural networks, such as the social decision making network in vertebrates (O'Connell and Hofmann, 2011, 20”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Goodson and Kabelik, 2009
Not checked in the free run.
- cites O'Connell and Hofmann, 2011, 2012
Not checked in the free run.
- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Interpretationown data
Sociosexual interaction and mating in male prairie voles is associated with robust, non-OT-dependent increases in neuronal activity and plasticity across the PBN.
“These results suggest that sociosexual interaction and mating in male prairie voles is associated with robust, non-OT-dependent increases in neuronal activity and plasticity across the PBN.”
Quote in the paperSubstantial claim - Premisecitation
A polymorphism in the OTR gene (Oxtr), which is robustly associated with patterns of OTR expression in the forebrain, predicts pair bonding behavior in male prairie voles.
“Furthermore, a polymorphism in the OTR gene (Oxtr), which is robustly associated with patterns of OTR expression in the forebrain, predicts pair bonding behavior in male prairie voles (King, et al., under review).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites King, et al., under review
Not checked in the free run.
- Premisecitation
A single pharmacological study using a less selective OTA and relatively small sample sizes (n=6-8 per group) failed to demonstrate an effect of OTA on male pair bonding.
“A single pharmacological study, using a less selective OTA and relatively small sample sizes for experimental groups (n=6-8 per group), failed to demonstrate an effect of OTA on male pair bonding (Winslow and Insel, 1993)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Winslow and Insel, 1993 source
Not checked in the free run.
- Interpretationown data
Central OTR signaling modulates sexual behavior in male prairie voles.
“suggesting that central OTR signaling modulates sexual behavior in male prairie voles.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Interpretationown data
This is the first conclusive, causal evidence demonstrating that endogenous OTR signaling modulates pair bonding in a male animal.
“To our knowledge, this is the first conclusive, causal evidence demonstrating that endogenous OTR signaling modulates pair bonding in a male animal.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- Interpretationown data
Fos induction within the MPOA reflects male sexual behavior in prairie voles.
“suggesting that, consistent with findings in other rodents, Fos induction within the MPOA reflects male sexual behavior in prairie voles.”
Quote in the paperSubstantial claim - Interpretationown data
Central OTR signaling during sociosexual interaction and mating with a female enhances functional connectivity across the PBN in male prairie voles.
“These analyses reveal an increase in correlated Fos expression across PBN nuclei in aCSF-treated subjects relative to both unexposed controls and OTA-treated subjects, consistent with the hypothesis that central OTR signaling during sociosexual interaction and mating with a female enhances functional connectivity across the PBN in male prairie voles.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
- The quote only partly states this claim. 1
- May combine two claims. 14
- Classified as probably not a substantial claim. 26
The quote only partly states this claim.
Findingown dataCentral oxytocin receptor signaling enhances correlated activation across sensory and reward processing brain areas during sociosexual interaction in male prairie voles.
“our data suggest that central OTR signaling during sociosexual interaction plays a critical role in modulating a robust pattern of correlated Fos expression across PBN nuclei.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThere was a significant main effect of treatment, but not brain region or interaction, on Fos expression in analyzed pair bonding network nuclei.
“A two-way repeated-measures ANOVA with treatment (aCSF-mated versus OTA-mated versus aCSF-unexposed subjects) as a between subjects factor and brain region as a within subjects factor revealed a significant main effect of treatment (F2,167=12.53; p=8.48×10-6; Eta-squared=0.08), but not brain region (F6,167=0.818; p=0.56; Eta-squared=0.02) or the interaction between treatment and brain region (F12,”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThere was a significant main effect of mating, but not treatment or interaction, on Fos expression within the medial preoptic area.
“A two-way ANOVA revealed a significant main effect of mating (F1,26=9.87; p=0.0042; Eta-squared=0.26), but not treatment (aCSF versus OTA; F1,26=0.956; p=0.34; Eta-squared=0.03) or the interaction between treatment and mating (F1,26=1.08; p=0.31; Eta-squared=0.03), on Fos expression within the MPOA.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationIn mammals, oxytocin modulates pair bonding behaviors in monogamous species.
“pair bonding behaviors in monogamous species (Hurlemann and Scheele, 2015; Johnson and Young, 2015; Ross and Young, 2009)”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Hurlemann and Scheele, 2015
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- cites Johnson and Young, 2015 source
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- cites Ross and Young, 2009
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Classified as probably not a substantial claim.
PremisecitationEndogenous vasopressin, and not oxytocin, regulated pair bonding in male prairie voles by acting at vasopressin 1a receptors in the ventral pallidum and lateral septum.
“It appeared that endogenous vasopressin, and not OT, regulated pair bonding in male prairie voles by acting at V1aR receptors in the ventral pallidum and lateral septum (Lim et al., 2004b; Lim and Young, 2004; Liu and Wang, 2003).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Lim et al., 2004b
Not checked in the free run.
- cites Lim and Young, 2004
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- cites Liu and Wang, 2003 source
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationExogenous central oxytocin infusions facilitate partner preference formation in both sexes.
“Although exogenous central OT infusions facilitate partner preference formation in both sexes (Cho et al., 1999)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cho et al., 1999 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOxytocin receptor signaling in the brain is critical for partner preference formation in female prairie voles.
“Early pharmacological studies revealed that OTR signaling in the brain is critical for partner preference formation in female prairie voles (Insel and Hulihan, 1995; Williams et al., 1994).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningCentral oxytocin receptor signaling facilitates social bond formation by coordinating activity across a pair bonding neural network.
“These results are consistent with the hypothesis that central OTR signaling facilitates social bond formation by coordinating activity across a pair bonding neural network.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Goodson and Kabelik, 2009
Not checked in the free run.
- cites Johnson and Young, 2015 source
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- cites Numan and Young, 2015
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationOxytocin mediates its central effects by binding with high affinity to oxytocin receptors and/or with lower affinity to vasopressin 1a receptors.
“OT mediates its central effects by binding with high affinity to OT receptors (OTRs) and/or with lower affinity to vasopressin 1a (V1aR) receptors (Schorscher-Petcu et al., 2010; Song et al., 2014).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S1 (asserted).
PremisecitationOxytocin facilitates social bonding behaviors by modulating neural transmission and encoding of social information across sensory and reward processing brain areas.
“It has been hypothesized that OT facilitates social bonding behaviors by modulating neural transmission and encoding of social information across sensory and reward processing brain areas (Johnson and Young, 2015; Numan and Young, 2015).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Johnson and Young, 2015 source
Not checked in the free run.
- cites Numan and Young, 2015
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Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationInvestigations in estralid finches found that the behavioral effects of central OT signaling on partner preference formation in males follows the same trend as in females, although it was not statistically significant within males only.
“For example, investigations in estralid finches have found that the behavioral effects of central OT signaling on partner preference formation in males follows the same trend as in females, although it was not statistically significant within males only (Klatt and Goodson, 2013).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Klatt and Goodson, 2013
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Classified as probably not a substantial claim. May combine two claims.
PremisecitationPrevious work suggested that the central OT system may modulate pair bonding in prairie voles in a sex-specific manner, with central OTRs modulating pair bonding in females but not in males.
“Previous work has suggested that the central OT system may modulate pair bonding in prairie voles in a sex-specific manner (Insel and Hulihan, 1995; Winslow and Insel, 1993), with central OTRs modulating pair bonding in females but not in males.”
Quote in the paperSubstantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationThe MeA, AON, PFC, NA, PVN and BLA are part of a hypothesized neural network underlying mating-induced pair bonds in prairie voles.
“The MeA, AON, PFC, NA, PVN and BLA are part of a hypothesized neural network underlying mating induced pair bonds in prairie voles (Johnson and Young, 2015; Numan and Young, 2015).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites Johnson and Young, 2015 source
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- cites Numan and Young, 2015
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Study design and conductown dataPrincipal component analyses used a permuted null distribution generated by 10,000 random assignments.
“This procedure was repeated 10,000 times and the p-value for the difference in variance explained was calculated as the proportion of permuted differences exceeding the initial observed difference value.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataFive subjects were excluded from analysis of Fos expression due to low perfusion quality.
“Five subjects (n=2 aCSF-treated, n=3 OTA treated) were excluded from analysis of Fos expression due to low perfusion quality.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataIntracerebroventricular cannula placement was verified by india ink staining of the entire ventricular system, and subjects with missed cannulations were excluded.
“To verify placement of the ICV injection cannula in animals subjected to a partner preference test, 10% india ink was injected at the time of euthanization and staining of the entire ventricular system was required for designation as correct placement. Based on this criterion, subjects with missed cannulations (n=6) were excluded from the analysis”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductown dataIn Experiment 2, cannula placement was verified on anti-Fos-immunostained sections, and all subjects had cannulation tracks continuous with the lateral intracerebral ventricles.
“location of the injection cannula was verified on anti-Fos-immunostained sections and subjects were included if the cannulation track was continuous with the lateral intracerebral ventricles. All subjects were found to have cannulation tracks that were continuous with the lateral intracerebral ventricles and were included in behavioral analysis.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown dataBehavioral scoring was performed by two independent scorers blind to treatment groups.
“Non-investigation, social investigation, mounting, and intromission behavior were quantified for male subjects using Observer XT 10 behavioral scoring software (Noldus Information Technology Inc.; Leesburg, VA) by two independent scorers blind to treatment groups.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn prairie voles, patterns of OTR expression across specific forebrain nuclei are associated with monogamous behavior and space use in males.
“In prairie voles, patterns of OTR expression across specific forebrain nuclei are associated with monogamous behavior and space use in males (Ophir et al., 2012)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ophir et al., 2012 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAlpha was adjusted to 0.007 to correct for multiple comparisons.
“α was adjusted to 0.007 to correct for the multiple comparisons.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim. May combine two claims.
InterpretationreasoningUnique OTR (and V1aR) expression patterns across the prairie vole forebrain may allow OT release during sociosexual interaction to trigger distinct, transient patterns of functional connectivity across the PBN that facilitate pair bond formation.
“Within this framework, unique OTR (and V1aR) expression patterns across the prairie vole forebrain may allow OT release during sociosexual interaction to trigger distinct, transient patterns of functional connectivity across the PBN that facilitate pair bond formation.”
Quote in the paperSubstantial claim- Rests on an assumption: Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
May combine two claims.
Interpretationown dataDifferences in Fos expression between OTA- and aCSF-treated groups are not likely due to differences in sensory or sexual stimulation, but more likely reflect differences in function and/or modulation of the PBN during equivalent sociosexual contexts.
“Thus, differences in Fos expression are not likely due to differences in sensory or sexual stimulation between treatment groups, but more likely reflect differences in function and/or modulation of the PBN during equivalent sociosexual contexts.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationIn male rats, hamsters, and gerbils, sexual behavior is associated with elevated Fos expression within the MPOA.
“In male rats (Robertson et al., 1991), hamsters (Kollack-Walker and Newman, 1997), and gerbils (Heeb and Yahr, 1996), sexual behavior is associated with elevated Fos expression within this nucleus.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Robertson et al., 1991 source
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- cites Kollack-Walker and Newman, 1997
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- cites Heeb and Yahr, 1996
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Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNeural investigations of sexual behavior have highlighted the hypothalamic MPOA as a deeply conserved neural locus regulating male sexual behavior across all vertebrate lineages.
“Neural investigations of sexual behavior have highlighted the hypothalamic MPOA as a deeply conserved neural locus regulating male sexual behavior across all vertebrate lineages (Dominguez and Hull, 2005).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Dominguez and Hull, 2005
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationIn rats, central administration of OTA reduces intromission frequency in males.
“In rats, central administration of OTA reduces intromission frequency in males (Argiolas et al., 1988).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Argiolas et al., 1988 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenDifferences in correlated patterns of Fos expression do not reveal how central OTR signaling modulates activity of specific neuronal phenotypes or dynamic electrophysiological network properties.
“First, differences in correlated patterns of Fos expression do not reveal how central OTR signaling modulates activity of specific neuronal phenotypes or dynamic electrophysiological network properties.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductreasoningThis behavioral paradigm included a diverse range of complex social interactions between the subject male and a unique stimulus female that varied across subjects; therefore, the behavioral specificity of these results is limited.
“Fourthly, this behavioral paradigm included a diverse range of complex social interactions between the subject male and a unique stimulus female (e.g. antagonistic interaction to intromission) that varied across subjects; therefore, the behavioral specificity of these results is limited.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationFos protein is encoded by the immediate early gene (IEG) c-fos and can heterodimerize with JUN to form AP-1 transcription factor complexes that directly up- or down-regulate expression of AP-1 responsive genes involved in a variety of intracellular processes, including synaptic plasticity.
“Briefly, Fos protein is encoded by the immediate early gene (IEG) c-fos and can heterodimerize with JUN to form AP-1 transcription factor complexes that directly up- or down-regulate expression of AP-1 responsive genes involved in a variety of intracellular processes, including synaptic plasticity (Lyons and West, 2011).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Lyons and West, 2011
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe resolution of the present study is limited to whole brain nuclei, each of which is composed of heterogeneous cell populations with diverse connectivities, properties, and functions.
“Thirdly, the resolution of the present study is limited to whole brain nuclei, each of which is composed of heterogeneous cell populations with diverse connectivities, properties, and functions.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Interpretationnone givenExogenous central OT delivery may not reflect endogenous central OT levels and can result in promiscuous signaling at both OTRs and V1aRs.
“However, it is important to note that these data are not necessarily contradictory, as exogenous central OT delivery may not reflect endogenous central OT levels and can result in promiscuous signaling at both OTRs and V1aRs.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationOT has deeply conserved roles in reproductive physiology and behavior across distant taxa spanning invertebrates and vertebrates, including mammalian species such as mice, rats, rabbits, and squirrel monkeys.
“OT has deeply conserved roles in reproductive physiology and behavior across distant taxa spanning invertebrates and vertebrates (Garrison et al., 2012), including mammalian species such as mice, rats, rabbits, and squirrel monkeys (Argiolas and Melis, 2004).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Garrison et al., 2012 source
Not checked in the free run.
- cites Argiolas and Melis, 2004
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe present study does not address whether or how social context is related to the neuromodulatory effects of increased central OTR signaling.
“Finally, the present study does not address whether or how social context is related to the neuromodulatory effects of increased central OTR signaling.”
Quote in the paperNot a substantial claimMay combine two claims.
Study design and conductreasoningRelatively small sample sizes, a high volume of pairwise comparisons, and brain-wide OTR blockade preclude conclusions about OTR-mediated disruptions in the functional relationships between specific PBN nuclei.
“Second, relatively small sample sizes, a high volume of pairwise comparisons, and brain-wide OTR blockade preclude conclusions about OTR-mediated disruptions in the functional relationships between specific PBN nuclei”
Quote in the paperNot a substantial claim
The paper relies on this without support.
Central delivery of an OTA specifically blocks endogenous signaling at central OTRs.
“In contrast, central delivery of an OTA specifically blocks endogenous signaling at central OTRs.”
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?
Endogenous central OTR signaling during sociosexual interaction strongly modulates patterns of correlated Fos-ir across SSN nuclei.
“but strongly modulates patterns of correlated Fos-ir across SSN nuclei”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
Previous experiments did not address the functional roles of region-specific OTR populations.
“These experiments, however, did not address the functional roles of region-specific OTR populations.”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
Endogenous central OTR signaling during sociosexual interaction does not strongly modulate levels of Fos-immunoreactivity (Fos-ir) within individual SSN nuclei.
“We previously found that endogenous central OTR signaling during sociosexual interaction does not strongly modulate levels of Fos-immunoreactivity (Fos-ir) within individual SSN nuclei”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
Sociosexual interaction and mating with a female was associated with a significant increase in Fos-ir across the SSN.
“This test confirmed that sociosexual interaction and mating with a female was associated with a significant increase in Fos-ir across the SSN (t1,25 = 4.49, p < 0.001), consistent with previous results (Johnson et al., 2016).”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
ICV administration of OTA reduces mating frequency in male prairie voles.
“We previously demonstrated that ICV administration of OTA reduces mating frequency in male prairie voles (Johnson et al., 2016).”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
In mated animals, OTA treatment in the NAc shell was associated with a non-significant trend toward increased Fos-ir compared to aCSF treatment.
“This analysis revealed a trend toward increased Fos-ir in OTA-treated compared to aCSF-treated subjects, although this trend was not statistically significant (t1,20 = 1.85, p = 0.08).”
From Oxytocin receptors modulate a social salience neural network in male prairie voles (2017) · cites this paper as Johnson et al., 2016
Central infusion of an OTR antagonist blocks the formation of partner preference in male prairie voles.
“central infusion of an OTR antagonist blocks the formation of partner preference in males”
From Oxytocin and Social Relationships: From Attachment to Bond Disruption (2017) · cites this paper as Johnson et al. 2016
Blocking brain oxytocin receptors in either sex prevents pair bonding, potentially disrupting coordinated activity across a social salience network.
“Blocking brain OXT receptors in either sex prevents pair bonding, potentially disrupting coordinated activity across a social salience network (137).”
From Oxytocin, Vasopressin, and Social Behavior: From Neural Circuits to Clinical Opportunities (2022) · cites this paper as [137]
Oxytocin enhances correlated activity across a network of social brain regions involved in pair-bonding in voles.
“which parallels findings in voles that show oxytocin enhances correlated activity across a network of social brain regions involved in pair-bonding [42].”
From Translational opportunities for circuit-based social neuroscience: advancing 21st century psychiatry (2021) · cites this paper as [42]
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.
Discussion gives a different p-value for the PBN Fos comparison
MinorThe discussion reports p=1.03×10-6 for the increase in Fos expression across PBN nuclei, while the results report p=3.20×10-5 for the comparison of mated animals with unexposed controls.
“Sociosexual interaction and mating with a female was associated with significantly elevated Fos expression across the analyzed PBN nuclei (p=1.03×10-6)”
“A one-way repeated measures ANOVA revealed a significant effect of sociosexual interaction and mating on Fos expression across the PBN between mated animals (pooled) and unexposed controls (F1,191=18.51; p=3.20×10-5; Eta-squared=0.07; Figure 4).”
Cited 1993 study does not match its description
MinorThe text describes Winslow and Insel (1993) as a study of an oxytocin receptor antagonist and male pair bonding, but the listed reference is titled as a study of vasopressin administration to infant rats.
“A single pharmacological study, using a less selective OTA and relatively small sample sizes for experimental groups (n=6-8 per group), failed to demonstrate an effect of OTA on male pair bonding (Winslow and Insel, 1993)”
“71. Winslow JT Insel TR 1993 Effects of central vasopressin administration to infant rats European journal of pharmacology 233 101 107 8472738”
The citation lists haven’t been fetched yet
References 80 · Cited by 190
Research works printed but not linked: 1
- Lim, 2004, Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene, Nature, 429, 754, 10.1038/nature02539 · DOI · Paper page
- Authors
- Johnson, Z. V., Walum, H., Jamal, Y. A., Xiao, Y., Keebaugh, A. C., Inoue, K., & Young, L. J.
- Affiliations
- Emory University (US)
- Corresponding author
- Johnson, Zachary V.
- Venue
- Hormones and Behavior
- Publisher
- Elsevier BV
- Published
- 2016-03
- Volume
- 79
- Pages
- 8-17
- ISSN
- 0018-506X (ISSN-L)
- PMC
- PMC4768463
- OpenAlex
- W2172896996
- Semantic Scholar
- 8559fc5c4533025f8568755e1dd84dcca4fcddf0
- Cited by
- 190
- References
- 80
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 9 · 2023: 5 · 2022: 14 · 2021: 17 · 2020: 23 · 2019: 5 · 2018: 72 · 2017: 13 · 2016: 14 · 2015: 1
- FWCI
- 54.68
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hormones and Behavior (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (R01MH096983, 1P50MH100023)
- Swedish Brain Foundation
- NIH Office of Research Infrastructure Programs (OD P51OD11132)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Sensory Systems › Olfactory and Sensory Function Studies
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Keywords
- oxytocin receptor, Microtus ochrogaster, mate preferences, pair bonding, social bonding, Fos expression, neuronal activation, forebrain, reward processing, male behavior, social monogamy
- MeSH terms
- Animals, Central Nervous System, Arvicolinae, Female, Humans, Male, Nerve Net, Oxytocin, Pair Bond, Prosencephalon, Receptors, Oxytocin, Mating Preference, Animal, Infusions, Intraventricular
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