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Oxytocin during Development: Possible Organizational Effects on Behavior
Open accessAbstract
Oxytocin (Oxt) is a neurohormone known for its physiological roles associated with lactation and parturition in mammals. Oxt can also profoundly influence mammalian social behaviors such as affiliative, parental, and aggressive behaviors. While the acute effects of Oxt signaling on adult behavior have been heavily researched in many species, including humans, the developmental effects of Oxt on the brain and behavior are just beginning to be explored. There is evidence that Oxt in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function. However, the specific mechanisms by which this occurs remain unknown. Thus, this review will detail what is known about how developmental Oxt impacts behavior as well as explore the specific neurochemicals and neural substrates that are important to these behaviors.
Overview
AI snapshot
Written from the paper’s full text.
TL;DR
This review argues that oxytocin (Oxt) can have organizational effects on behavior, not just acute neuromodulatory effects, based on developmental manipulations in rodents, voles, pigs, and mice. It summarizes behavioral and neurochemical evidence from early postnatal, peripubertal, and possible fetal windows, while emphasizing that mechanisms remain unknown.
Key findings
- A single intracisternal Oxt injection on postnatal day (PND) 3 in rats significantly increased novelty-induced grooming at 4 months of age; later work found developmental Oxt manipulation affects social, sexual, aggressive, parental, and other behaviors across species.
- In prairie voles, PND0 Oxt (3.0 μg i.p.) increased adult female intrasexual aggression, while in males low (1 mg/kg) and high (4 mg/kg) doses increased partner preference and social contact, but 2 mg/kg did not.
- Neonatal OTA treatment in mice decreased social approach in females tested at 8–15 weeks but had no effect in males; in male prairie voles, neonatal OTA decreased alloparental behavior at PND21 but not at PND60.
- Developmental Oxt altered neurochemical systems: neonatal Oxt increased estrogen receptor α expression in the ventromedial hypothalamus and other regions, and Oxt/OTA had sexually dimorphic effects on vasopressin 1a receptor binding; fetal Oxtr knockout mice showed heightened adult aggression.
Methods
- Narrative review synthesizing published animal studies on developmental Oxt manipulation and later behavior, including a summary table of designs and findings across prairie voles, mandarin voles, rats, mice, and pigs.
- The reviewed studies used neonatal or peripubertal Oxt or Oxt receptor antagonist (OTA) administration, intranasal Oxt, viral vector overexpression, and genetic knockout models, with behavioral assays at later ages.
- No primary data collection or formal meta-analysis is reported; the paper integrates behavioral and neurochemical findings to propose organizational effects.
Limitations
- The paper states that specific mechanisms by which developmental Oxt alters neural structure and function remain unknown, and that there is a lack of consensus in the data due to differences in timing, dose, and behavioral endpoints.
- The paper states that Oxt’s organizational effects appear sex- and species-specific, that fetal development is largely unexplored, and that the developmental time course of the Oxt system in rodents is poorly known.
- Evident from the text: as a narrative review, it does not use a systematic search or quantitative synthesis, and many summarized findings are from small or non-replicated studies, with some table entries marked “ND” (no data).
Model-written summary. Check it against the paper before relying on it.
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Claims the paper makes
0 of 129 cited sources checked · 0 supported · 0 flagged
- Premisecitation
A single intracisternal injection of oxytocin in postnatal day 3 rats significantly increases novelty-induced grooming at 4 months of age.
“Their work demonstrated that a single intracisternal injection of Oxt in postnatal day (PND) 3 rats (Rattus norvegicus) significantly increases novelty-induced grooming at 4 months of age (10)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] Noonan, 1989, Neonatal administration of oxytocin increases novelty-induced grooming in the adult rat, Pharmacol Biochem Behav source
- Premisecitation
Exposure to oxytocin during early life is important for the proper development of neural pathways and subsequent sex-specific behaviors.
“While much of the work on Oxt has focused on its involvement in the acute modulation of behavior, there is also evidence that exposure to Oxt during early life is important for the proper development of neural pathways and subsequent sex-specific behaviors.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Boer and colleagues failed to replicate the finding that neonatal oxytocin increases novelty-induced grooming in an open-field test.
“However, when a study by Boer and colleagues failed to replicate the aforementioned findings in an open-field test (12), investigations into the organizational effects of Oxt largely fell by the wayside.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [12] Boer, 1994, Mild sustained effects of neonatal vasopressin and oxytocin treatment on brain growth and behavior of the rat, Peptides source
- Premisecitation
Oxytocin has central neuromodulatory effects on social behaviors such as affiliative, aggressive, and parental behaviors.
“Oxytocin is a mammalian neurohormone composed of nine amino acids, known for its peripheral effects on parturition and lactation (5–7), as well as its central neuromodulatory effects on social behaviors such as affiliative, aggressive, and parental behaviors (8, 9).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
There is evidence that oxytocin in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function.
“There is evidence that Oxt in early postnatal and peripubertal development, and perhaps during prenatal life, affects adult behavior by altering neural structure and function.”
Quote in the paperSubstantial claim0 of 2 sources checked
- Interpretationcitation
Studies in numerous species provide converging evidence that oxytocin during development can have permanent effects on the brain and behavior.
“Yet, in the last 12 years, there has been a resurgence of research in this area, with studies in numerous species providing converging evidence that Oxt during development can have permanent effects on the brain and behavior (3, 13–29) (see Table 1).”
Quote in the paperSubstantial claim0 of 10 sources checked- cites [3] Cushing, 2013, The organizational effects of oxytocin and vasopressin source
- cites [13] Bales, 2004, Both oxytocin and vasopressin may influence alloparental behavior in male prairie voles, Horm Behav source
- cites [14] Bales, 2004, Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles, Dev Psychobiol source
- cites [15] Bales, 2007, Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors, Neuroscience source
- cites [16] Bales, 2007, Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles, Horm Behav source
- cites [17] Bales, 2004, Effects of neonatal oxytocin manipulations on male reproductive potential in prairie voles, Physiol Behav source
- cites [18] Bales, 2003, Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster), Horm Behav source
- cites [19] Bales, 2003, Developmental exposure to oxytocin facilitates partner preferences in male prarie voles (Microtus ochrogaster), Behav Neurosci source
- cites [20] Cushing, 2005, Neonatal manipulation of oxytocin influences female reproductive behavior and success, Horm Behav source
- cites [21] Eaton, 2012, Organizational effects of oxytocin on serotonin innervation, Dev Psychobiol source
- Premisecitation
The organizational/activational hypothesis has been extended to include puberty and other hormones, including oxytocin.
“Given the importance of this concept, it is perhaps not surprising that in the last 55 years this hypothesis has been extended to include another critical time period – puberty – as well as other hormones and behaviors, with one of these hormones being oxytocin (Oxt) (2–4).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [2] Schulz, 2009, Back to the future: the organizational-activational hypothesis adapted to puberty and adolescence, Horm Behav source
- cites [3] Cushing, 2013, The organizational effects of oxytocin and vasopressin source
- cites [4] Bouret, 2013, Organizational actions of metabolic hormones, Front Neuroendocrinol source
- Premisecitation
Male mandarin voles that receive a single postnatal injection of oxytocin increase their mounting behavior at postnatal day 60.
“Male mandarin voles that receive a single postnatal injection of Oxt increase their mounting behavior at PND60 (37).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [37] Jia, 2008, Neonatal manipulation of oxytocin influences the partner preference in mandarin voles (Microtus mandarinus), Neuropeptides source
- Premisecitation
Male mice administered an oxytocin receptor antagonist on postnatal day 0 display social approach behaviors similar to controls.
“On the other hand, male mice administered an OTA on PND0 display social approach behaviors similar to what is observed in the control conditions (29).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] Mogi, 2014, Effects of neonatal oxytocin manipulation on development of social behaviors in mice, Physiol Behav source
- Premisecitation
In prairie voles, injection of both oxytocin and an oxytocin receptor antagonist on postnatal day 1 decreases the frequency of mating bouts in adult males and females.
“whereas an injection of both Oxt and an Oxt receptor antagonist (OTA), also on PND1, decreases the frequency of mating bouts in both adult males and females (20).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [20] Cushing, 2005, Neonatal manipulation of oxytocin influences female reproductive behavior and success, Horm Behav source
- Premisecitation
Female mice administered an oxytocin receptor antagonist (3 μg/20 μL) on the day of birth have decreases in social approach when tested at 8-15 weeks.
“Female mice administered an OTA (3 μg/20 μL) on the day of birth have decreases in social approach when tested at 8–15 weeks (29)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] Mogi, 2014, Effects of neonatal oxytocin manipulation on development of social behaviors in mice, Physiol Behav source
- Premisecitation
A single postnatal injection of oxytocin increases intrasexual aggression in adult female mandarin voles after exposure to a male.
“A single postnatal injection of Oxt also increases intrasexual aggression in adult female mandarin voles (Lasiopodomys mandarinus) after exposure to a male (35).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [35] Jia, 2008, Effects of neonatal oxytocin treatment on aggression and neural activities in mandarin voles, Physiol Behav source
- Premisecitation
In male prairie voles, injection of oxytocin at low (1 mg/kg) and high (4 mg/kg) doses on postnatal day 0 increases partner preference and social contact in adults compared to controls.
“In male prairie voles, an injection of Oxt at both low (1 mg/kg) and high (4 mg/kg) doses on PND0 increases partner preference and social contact in adults compared to controls (19, 36);”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationcitation
Oxytocin's developmental effects on sociability may extend into peripubertal development.
“There is also evidence that Oxt’s developmental effects on sociability may not be limited to the perinatal period, but may also extend into peripubertal development (2).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [2] Schulz, 2009, Back to the future: the organizational-activational hypothesis adapted to puberty and adolescence, Horm Behav source
- Premisecitation
Injecting an adeno-associated viral vector overexpressing the oxytocin receptor into the nucleus accumbens shell of female prairie voles at postnatal day 21 facilitates alloparental care, as measured by reductions in approach times and increases in time spent licking and grooming pups compared to controls.
“By injecting an adeno-associated viral vector into the nucleus accumbens (NAcc) shell of female prairie voles at PND21 they were able to facilitate alloparental care, as measured by reductions in approach times and increases in time spent licking and grooming pups compared to controls (57).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [57] Keebaugh, 2011, Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults, Horm Behav source
- Premisecitation
Male prairie voles administered low, medium, and high doses of intranasal oxytocin daily from postnatal day 21 to 42 display increases in social contact during the treatment window.
“Male prairie voles administered low, medium, and high doses of intranasal Oxt daily during the approximate time between weaning and sexual maturity, from PND21 until 42, display increases in social contact during the treatment window”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [43] Bales, 2013, Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles, Biol Psychiatry source
- Premisecitation
Male prairie voles given low and medium doses of intranasal oxytocin from postnatal day 21 to 42 increase their preference for strangers when tested from postnatal day 43 to 60.
“and those given low and medium doses increase their preference for strangers when tested from PND43–60 (43).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [43] Bales, 2013, Chronic intranasal oxytocin causes long-term impairments in partner preference formation in male prairie voles, Biol Psychiatry source
- Premisecitation
Chronic intranasal oxytocin from 12 to 23 weeks reduced social behavior in adult male mice when they were tested 1 hour after oxytocin administration.
“Another study found that chronic intranasal Oxt from 12 to 23 weeks reduced social behavior in adult male mice when they were tested 1 h after Oxt administration (45).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] Huang, 2014, Chronic and acute intranasal oxytocin produce divergent social effects in mice, Neuropsychopharmacology source
- Premisecitation
Male rats given oxytocin injections every 3 days from postnatal day 28 to 55 spent more time in close proximity to conspecifics than control animals when tested at postnatal day 70.
“When tested in a social interaction test at PND70, their behavior appeared similar to what was described above, with their spending more time in close proximity to conspecifics than control animals (42).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [42] Suraev, 2014, Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood, Horm Behav source
- Premisecitation
In male prairie voles, treatment with an oxytocin receptor antagonist in neonates decreases alloparental behaviors, as measured by fewer retrievals, less time spent huddling over pups, and increases in pup-directed attacks when tested on postnatal day 21.
“Specifically, males injected with an OTA within 24 h of birth and later tested on PND21 decrease their parental care, as measured by fewer retrievals, less time spent huddling over pups, and increases in pup-directed attacks.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] Bales, 2004, Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles, Dev Psychobiol source
- Interpretationreasoning
Intranasal oxytocin treatment during peripubertal development facilitates social interactions in both males and females.
“While the studies described above may differ somewhat in terms of the details of their findings, it does appear that intranasal Oxt treatment during peripubertal development facilitates social interactions in both males and females.”
Quote in the paperSubstantial claim - Interpretationreasoning
Oxytocin signaling is important for normal displays of alloparental care.
“Thus, it appears that Oxt signaling is important for normal displays of alloparental care, which is consistent with its role in lowering the threshold for maternal care in rodents (53–56).”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [53] Rich, 2014, Impairments in the initiation of maternal behavior in oxytocin receptor knockout mice, PLoS One source
- cites [54] Macbeth, 2010, Normal maternal behavior, but increased pup mortality, in conditional oxytocin receptor knockout females, Behav Neurosci source
- cites [55] Pedersen, 1997, Oxytocin control of maternal behavior. Regulation by sex steroids and offspring stimuli, Ann N Y Acad Sci source
- cites [56] Francis, 2002, Naturally occurring differences in maternal care are associated with the expression of oxytocin and vasopressin (V1a) receptors: gender differences, J Neuroendocrinol source
- Premisecitation
Oxytocin and oxytocin receptor knockout mice develop late-onset obesity in the absence of hyperphagia.
“These mice develop late-onset obesity in the absence of hyperphagia (65, 66).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Gonadal steroids play a significant role in regulating oxytocin activity.
“It is well established that gonadal steroids play a significant role in regulating Oxt activity (68–71).”
Quote in the paperNot a substantial claim0 of 4 sources checked- cites [68] Gimpl, 2001, The oxytocin receptor system: structure, function, and regulation, Physiol Rev source
- cites [69] Dhakar, 2013, Oxytocin, vasopressin and their interplay with gonadal steroids source
- cites [70] Caldwell, 2006, Oxytocin and vasopressin: genetics and behavioral implications source
- cites [71] Tribollet, 1990, Gonadal steroids regulate oxytocin receptors but not vasopressin receptors in the brain of male and female rats. An autoradiographical study, Brain Res source
- Interpretationcitation
The nucleus accumbens is a specific neural substrate on which oxytocin may act to affect alloparental care.
“This gene delivery approach has helped to identify a specific neural substrate – the NAcc – on which Oxt may act.”
Quote in the paperSubstantial claim - Interpretationreasoning
Oxytocin's organizational effects appear to be sex- and species-specific.
“It is also important to note that Oxt’s organizational effects appear to be sex- and species-specific, which is consistent with the complexity of its neuromodulatory role in adulthood.”
Quote in the paperSubstantial claim - Premisecitation
In female prairie voles, oxytocin treatment on postnatal day 0 decreases vasopressin 1a receptor binding in the medial preoptic area, BNST, lateral septum, cingulate cortex, and medial thalamus on postnatal day 60.
“Specifically, in female prairie voles, Oxt treatment on PND0 decreases Avpr1a binding in the MPOA, BNST, LS, cingulate cortex (CgCtx), and medial thalamus on PND60”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Bales, 2007, Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors, Neuroscience source
- Premisecitation
Early exposure to relevant stimuli permanently alters the responsiveness of a hormone receptor, a phenomenon known as hormonal imprinting.
“Early exposure to relevant stimuli is known to permanently alter the responsiveness of a hormone receptor; this phenomenon is known as hormonal imprinting (80).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [80] Csaba, 1980, Phylogeny and ontogeny of hormone receptors: the selection theory of receptor formation and hormonal imprinting, Biol Rev source
- Premisecitation
In female prairie voles, neonates treated with oxytocin and an oxytocin receptor antagonist have increases in oxytocin immunoreactivity within the paraventricular nucleus by 3 weeks of age.
“In female prairie voles, neonates treated with Oxt and an OTA have increases in Oxt immunoreactivity (Oxt-ir) within the PVN by 3 weeks of age.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Yamamoto, 2004, Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner, Neuroscience source
- Premisecitation
Rats repeatedly administered oxytocin from postnatal day 0 until postnatal day 7 have increases in estrogen receptor alpha immunoreactivity at postnatal day 75.
“Similar to prairie voles, rats that are repeatedly administered Oxt from PND0 until PND7 have increases in ERα-ir at PND75 (28)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [28] Perry, 2009, Neonatal oxytocin alters subsequent estrogen receptor alpha protein expression and estrogen sensitivity in the female rat, Behav Brain Res source
- Premisecitation
Neonatal oxytocin manipulation increases the expression of estrogen receptor alpha in the hippocampus, ventral lateral septum, and central nucleus of the amygdala.
“and neonatal Oxt manipulation increases the expression of ERα in the hippocampus (79), ventral lateral septum (LS), and central nucleus of the amygdala (24).”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [79] Pournajafi-Nazarloo, 2007, Oxytocin selectively increases ERα mRNA in the neonatal hypothalamus and hippocampus of female prairie voles, Neuropeptides source
- cites [24] Kramer, 2007, The organizational effects of oxytocin on the central expression of estrogen receptor alpha and oxytocin in adulthood, BMC Neurosci source
- Premisecitation
Maternal physiology, particularly stress and nutrition, can greatly impact the neural and behavioral development of offspring.
“This is in keeping with a large body of research showing that maternal physiology, particularly stress (85–87) and nutrition (88–90), can greatly impact the neural and behavioral development of offspring.”
Quote in the paperNot a substantial claim0 of 6 sources checked- cites [85] Ward, 2013, Transgenerational programming of maternal behaviour by prenatal stress, BMC Pregnancy Childbirth source
- cites [86] Fine, 2014, Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders, Mol Psychiatry source
- cites [87] DiPietro, 2012, Maternal stress in pregnancy: considerations for fetal development, J Adolesc Health source
- cites [88] Reyes-Castro, 2012, Pre-and/or postnatal protein restriction developmentally programs affect and risk assessment behaviors in adult male rats, Behav Brain Res source
- cites [89] Peleg-Raibstein, 2012, Maternal high-fat diet in mice programs emotional behavior in adulthood, Behav Brain Res source
- cites [90] Marques, 2013, The influence of maternal prenatal and early childhood nutrition and maternal prenatal stress on offspring immune system development and neurodevelopmental disorders, Front Neurosci source
- Premisecitation
In male prairie voles, oxytocin treatment on postnatal day 0 increases vasopressin 1a receptor binding in the cingulate cortex.
“but in males it increases Avpr1a binding in the CgCtx.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Bales, 2007, Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors, Neuroscience source
- Interpretationreasoning
Delivery of oxytocin or an oxytocin receptor antagonist during early postnatal life appears to have nearly opposite effects on adult vasopressin 1a receptor expression in females and males.
“Taken together, the delivery of Oxt or an OTA during early postnatal life appears to have nearly opposite effects on adult Avpr1a expression in females and males.”
Quote in the paperSubstantial claim - Premisecitation
In female prairie voles, oxytocin receptor antagonist treatment decreases vasopressin 1a receptor binding only in the BNST and cingulate cortex.
“OTA treatment in females decreases Avpr1a binding only in the BNST and CgCtx”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Bales, 2007, Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors, Neuroscience source
- Premisecitation
Pigs that receive oxytocin have less blunting of the cortisol response than controls.
“However, pigs that receive Oxt have less blunting of the cortisol response than controls (39).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Rault, 2013, Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior, Physiol Behav source
- Premisecitation
In male prairie voles, neonatal oxytocin administration results in increases in serotonergic axon density in the anterior hypothalamus, cortical amygdala, and ventromedial hypothalamus at postnatal day 21.
“In male prairie voles, neonatal Oxt administration also results in increases in serotonergic axon density in the anterior hypothalamus, cortical amygdala, and VMH at PND21 (21)”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [21] Eaton, 2012, Organizational effects of oxytocin on serotonin innervation, Dev Psychobiol source
- Premisecitation
In male prairie voles, oxytocin receptor antagonist treatment decreases vasopressin 1a receptor binding in the medial preoptic area, BNST, and lateral septum.
“while in males it decreases Avpr1a binding in the MPOA, BNST, and LS (15).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [15] Bales, 2007, Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors, Neuroscience source
- Premisecitation
Female prairie voles administered oxytocin on postnatal day 1 have reductions in baseline plasma corticosterone by postnatal day 8 compared to animals treated with saline or an oxytocin receptor antagonist.
“Female prairie voles administered Oxt on PND1 have reductions in baseline plasma corticosterone by PND8 compared to animals treated with saline or an OTA (23).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [23] Kramer, 2003, Developmental effects of oxytocin on stress response: single versus repeated exposure, Physiol Behav source
- Premisecitation
In mice, in utero exposure to Oxt is important for normal intermale aggressive behavior in adulthood.
“In mice, there is evidence that in utero exposure to Oxt is important for normal intermale aggressive behavior in adulthood.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Work from Bruce Cushing's laboratory suggests that the BNST and medial amygdala are particularly important for the developmental effects of oxytocin and estrogen receptor alpha on social behavior.
“Work from Bruce Cushing’s laboratory suggests that the BNST and MeA are particularly important for the developmental effects of Oxt and ERα on social behavior (24, 26, 94)”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [24] Kramer, 2007, The organizational effects of oxytocin on the central expression of estrogen receptor alpha and oxytocin in adulthood, BMC Neurosci source
- cites [26] Yamamoto, 2006, Neonatal manipulation of oxytocin affects expression of estrogen receptor alpha, Neuroscience source
- cites [94] Cushing, 2005, Mechanisms underlying epigenetic effects of early social experience: the role of neuropeptides and steroids, Neurosci Biobehav Rev source
- Premisecitation
The heightened aggressive behavior phenotype of male Oxt−/− mice born to null mutant dams cannot be rescued by cross-fostering to wild-type dams.
“While this phenotype cannot be rescued if the pups are cross-fostered to wild-type dams (99), it is not observed when male mice are born to heterozygous dams.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [99] Takayanagi, 2005, Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice, Proc Natl Acad Sci U S A source
- Premisecitation
Male Oxt−/− mice born to null mutant dams show heightened aggressive behavior in adulthood.
“Specifically, male Oxt−/− mice that are born to null mutant dams show heightened aggressive behavior in adulthood (97, 98).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Increased use of oxytocin receptor agonists such as Pitocin and antagonists such as Atosiban during human pregnancy to manage labor timing makes potential fetal oxytocin effects relevant.
“These potential effects are relevant, in part, because of the increased use of Oxtr agonists, such as Pitocin, and antagonists, such as Atosiban, during human pregnancy in order to manage labor timing (95, 96).”
Quote in the paperSubstantial claim0 of 2 sources checked - Interpretationreasoning
The brain regions most commonly affected by developmental oxytocin exposure are the ventromedial hypothalamus, medial preoptic area, BNST, lateral septum, paraventricular nucleus, and several nuclei of the amygdala.
“The brain regions most commonly affected by developmental Oxt exposure are the VMH, MPOA, BNST, LS, PVN, and several nuclei of the amygdala.”
Quote in the paperSubstantial claim - Interpretationreasoning
The key difference between pups born to null mutant dams and those born to heterozygous dams is the absence or presence of maternal Oxt.
“One of the key differences between pups born to null mutant dams versus those born to heterozygous dams is the absence or presence of maternal Oxt.”
Quote in the paperSubstantial claim- Rests on an assumption: The heightened aggressive behavior phenotype is not observed when male mice are born to heterozygous dams.
- Interpretationreasoning
The organizational effects of oxytocin extend to many different neurochemical systems including the gonadal steroids, the oxytocin and vasopressin systems, and the stress axis.
“The organizational effects of Oxt extend to many different neurochemical systems including the gonadal steroids, the Oxt and Avp systems, and the stress axis, which suggests that Oxt’s effects are widespread and complex (Figure 1).”
Quote in the paperSubstantial claim - Premisecitation
Male forebrain Oxtr knockout mice, in which the Oxtr gene is excised 21-28 days after birth, have normal aggressive behavior in adulthood.
“However, male forebrain Oxtr knockout (Oxtr Fb/Fb) mice (101, 102), in which the Oxtr gene is excised 21–28 days after birth, have normal aggressive behavior in adulthood (100).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [100] Dhakar, 2012, Heightened aggressive behavior in mice with lifelong versus postweaning knockout of the oxytocin receptor, Horm Behav source
- cites [101] Lee, 2008, A conditional knockout mouse line of the oxytocin receptor, Endocrinology source
- cites [102] Lee, 2008, Behavioural studies using temporal and spatial inactivation of the oxytocin receptor, Prog Brain Res source
- Interpretationcitation
Studies using male Oxtr knockout mice support the hypothesis that maternal Oxt may be signaling in the fetal brain.
“The hypothesis that the maternal Oxt may be signaling in the fetal brain is supported by studies using male Oxtr knockout (Oxtr−/−) mice, which lack Oxtr signaling throughout development.”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
Male Oxtr knockout mice have heightened aggressive behavior in adulthood.
“These mice also have heightened aggressive behavior in adulthood (99, 100).”
Quote in the paperSubstantial claim0 of 2 sources checked - Premisecitation
The mRNA for the Oxt carrier protein neurophysin-I is available as early as E16 in the PVN and SON.
“The mRNA for the Oxt carrier protein neurophysin-I is available as early as E16 in the PVN and SON, and the Oxt peptide is seen by PND7 in the SON and PVN and E21 in the pituitary (104).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] Whitnall, 1985, Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons, J Neurosci source
- Premisecitation
The Oxt peptide is seen by E21 in the pituitary.
“The mRNA for the Oxt carrier protein neurophysin-I is available as early as E16 in the PVN and SON, and the Oxt peptide is seen by PND7 in the SON and PVN and E21 in the pituitary (104).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] Whitnall, 1985, Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons, J Neurosci source
- Premisecitation
A study by Hammock and Levitt found Oxtr binding in the brains of E18.5 C57BL/6J mice.
“In mice, a study by Hammock and Levitt (105), which focused primarily on Oxtr binding during postnatal development, found Oxtr binding in the brains of E18.5 C57BL/6J mice.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [105] Hammock, 2013, Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse, Front Behav Neurosci source
- Premisecitation
In rats, Oxtr binding has been identified as early as E14 in undifferentiated neurons.
“While less is known about the development of the Oxtr, in rats, Oxtr binding has been identified as early as E14 in undifferentiated neurons (104).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] Whitnall, 1985, Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons, J Neurosci source
- Premisecitation
The study by Hammock and Levitt examined only one embryonic time point.
“However, this was the only embryonic time point that was examined.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [105] Hammock, 2013, Oxytocin receptor ligand binding in embryonic tissue and postnatal brain development of the C57BL/6J mouse, Front Behav Neurosci source
- Premisecitation
The Oxt peptide is seen by PND7 in the SON and PVN.
“The mRNA for the Oxt carrier protein neurophysin-I is available as early as E16 in the PVN and SON, and the Oxt peptide is seen by PND7 in the SON and PVN and E21 in the pituitary (104).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [104] Whitnall, 1985, Neurophysin in the hypothalamo-neurohypophysial system. II. Immunocytochemical studies of the ontogeny of oxytocinergic and vasopressinergic neurons, J Neurosci source
- Interpretationnone given
Very little is known about the developmental time course of the Oxt system in rodents.
“Unfortunately, very little is known about the developmental time course of the Oxt system in rodents.”
Quote in the paperNot a substantial claim
- Probably not a substantial claim. 7
- It may state two separate claims as one. 33
- The quote only partly states this claim. 1
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationOxytocin has peripheral effects on parturition and lactation.
“Oxytocin is a mammalian neurohormone composed of nine amino acids, known for its peripheral effects on parturition and lactation (5–7), as well as its central neuromodulatory effects on social behaviors such as affiliative, aggressive, and parental behaviors (8, 9).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [5] Blanks, 2003, The role of oxytocin in parturition, BJOG source
- cites [6] Wakerley, 1973, The milk-ejection reflex of the rat: a 20-to 40-fold acceleration in the firing of paraventricular neurones during oxytocin release, J Endocrinol source
- cites [7] Frayne, 1996, Effects of oxytocin on sperm transport in the pubertal rat, J Reprod Fertil source
Probably not a substantial claim.
PremisecitationPerinatal exposure to gonadal steroids is important for the sexual differentiation of the brain and behavior.
“This hypothesis, which states that perinatal exposure to gonadal steroids is important for the sexual differentiation of the brain and behavior, is part of the foundation on which the field of behavioral neuroendocrinology has been built.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [1] Phoenix, 1959, Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig, Endocrinology source
It may state two separate claims as one. The quote only partly states this claim.
InterpretationreasoningBecause the pig study is the only one to use an ungulate animal model and one of only a few to use intranasal oxytocin administration, it is not known if these findings are broadly applicable to other species.
“Because of the uniqueness of this species, it is not known if these findings are broadly applicable to other species.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationPostnatal intranasal oxytocin administration in 2.5- to 8-week-old pigs increases intrasexual aggressive behavior and decreases social contact.
“Postnatal intranasal Oxt administration in 2.5- to 8-week-old pigs (Sus scrofa) increases intrasexual aggressive behavior and decreases social contact (39)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [39] Rault, 2013, Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior, Physiol Behav source
It may state two separate claims as one.
PremisecitationIn female prairie voles, a single injection of oxytocin on postnatal day 1 results in increases in intrasexual aggression in adults, suggesting strengthened pair bond formation.
“In female prairie voles, a single injection of Oxt on PND1 results in increases in intrasexual aggression in adults, suggesting strengthened pair bond formation (18)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [18] Bales, 2003, Sex differences and developmental effects of oxytocin on aggression and social behavior in prairie voles (Microtus ochrogaster), Horm Behav source
It may state two separate claims as one.
PremisecitationIn male prairie voles, oxytocin at 2 mg/kg on postnatal day 0 does not increase partner preference and social contact.
“however, a dose of 2 mg/kg does not (36).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36] Carter, 2008, Early experience and the developmental programming of oxytocin and vasopressin source
It may state two separate claims as one.
InterpretationreasoningIn mice, oxytocin exposure in neonate females may promote affiliative behaviors, while having no effect in males.
“So, in mice it appears that Oxt exposure in neonate females may promote affiliative behaviors, while having no effect in males.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationMale rats administered daily oxytocin injections from postnatal day 33 to 42 spent more time in close proximity to conspecifics and made more active social contacts than controls when tested on postnatal day 55.
“Oxt-treated males spent more time in close proximity to conspecifics and made more active social contacts than controls (41).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] Bowen, 2011, Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats, PLoS One source
It may state two separate claims as one.
PremisecitationThe effects of neonatal oxytocin receptor antagonist treatment on male prairie vole alloparental behaviors are transient and are not observed when the same animals are tested again on postnatal day 60.
“These effects also appear to be transient, as they are not observed when the same animals are tested again on PND60 (14).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [14] Bales, 2004, Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles, Dev Psychobiol source
It may state two separate claims as one.
PremisecitationOxytocin treatment increases the responsiveness of female mice to pups, as measured by approach times, in a dose-dependent manner, with the lowest dose resulting in longer approach times compared to saline controls.
“Oxt treatment also increases the responsiveness of females to pups, as measured by approach times, although this effect is dose dependent, with the lowest dose of Oxt resulting in longer approach times compared to saline controls (16).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [16] Bales, 2007, Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles, Horm Behav source
It may state two separate claims as one.
PremisecitationIn laboratory mice, treatment with an oxytocin receptor antagonist on postnatal day 0 decreases the total number of pups retrieved by females and increases pup retrieval latencies in males.
“Specifically, treatment with an OTA on PND0 decreases the total number of pups retrieved by females and increases pup retrieval latencies in males (29).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [29] Mogi, 2014, Effects of neonatal oxytocin manipulation on development of social behaviors in mice, Physiol Behav source
It may state two separate claims as one.
PremisecitationAndrogens and progesterone modulate oxytocin and oxytocin receptor expression, while estrogens seem to have the greatest impact on the oxytocin system.
“While androgens and progesterone modulate Oxt and Oxtr expression (72–75), it is the estrogens that seem to have the greatest impact on the Oxt system (68, 70, 74, 76–78).”
Quote in the paperNot a substantial claim0 of 9 sources checked- cites [72] Johnson, 1991, The regulation of oxytocin receptor binding in the ventromedial hypothalaimic nucleus by testosterone and its metabolites, Endocrinology source
- cites [73] Bale, 1995, Regulation of oxytocin receptor messenger ribonucleic acid in the ventromedial hypothalamus by testosterone and its metabolites, Endocrinology source
- cites [74] Wathes, 1996, Regulation of oxytocin, oestradiol and progesterone receptor concentrations in different uterine regions by oestradiol, progesterone and oxytocin in ovariectomized ewes, J Endocrinol source
- cites [75] Grazzini, 1998, Inhibition of oxytocin receptor function by direct binding of progesterone, Nature source
- cites [68] Gimpl, 2001, The oxytocin receptor system: structure, function, and regulation, Physiol Rev source
- cites [70] Caldwell, 2006, Oxytocin and vasopressin: genetics and behavioral implications source
- cites [76] De Kloet, 1986, Estradiol modulates density of putative oxytocin receptors’ in discrete rat brain regions, Neuroendocrinology source
- cites [77] Richard, 1990, The human oxytocin gene promoter is regulated by estrogens, J Biol Chem source
- cites [78] McCarthy, 1997, An anxiolytic action of oxytocin is enhanced by estrogen in the mouse, Physiol Behav source
It may state two separate claims as one.
PremisecitationIn rats, repeated administration of oxytocin between postnatal day 10 and 14 results in weight gain in both males and females, increases in the gut hormone cholecystokinin, and longer withdrawal latencies in the tail-flick test at postnatal day 60, suggesting an increase in pain threshold.
“In rats, repeated administration of Oxt between PND10 and PND14 results in weight gain in both males and females, increases in the gut hormone cholecystokinin, and longer withdrawal latencies in the tail-flick test at PND60, which suggests an increase in pain threshold (63).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [63] Uvnäs-Moberg, 1998, Postnatal oxytocin injections cause sustained weight gain and increased nociceptive thresholds in male and female rats, Pediatr Res source
It may state two separate claims as one.
PremisecitationMale rats given daily oxytocin injections from postnatal day 33 to 42 consumed significantly less alcohol than controls when tested on postnatal day 72 and later, while water consumption remained unaffected.
“When tested on PND72 and later, Oxt-treated males consumed significantly less alcohol (i.e., beer) than controls, while water consumption remained unaffected (41).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] Bowen, 2011, Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats, PLoS One source
It may state two separate claims as one.
PremisecitationMale rats given daily oxytocin injections from postnatal day 33 to 42 and tested in an emergence test on postnatal day 50 traveled further and spent more time in the open-field compared to controls, suggesting that oxytocin had an anxiolytic effect.
“Male rats given daily Oxt injections from PND33 to PND42 and tested in an emergence test on PND50 traveled further and spent more time in the open-field compared to controls, which would suggest that Oxt had an anxiolytic effect.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [41] Bowen, 2011, Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats, PLoS One source
It may state two separate claims as one.
PremisecitationMice with a genetic disruption that models Prader-Willi syndrome usually exhibit a lethal feeding deficiency; this deficiency can be rescued with an injection of oxytocin on postnatal day 0, or induced in wild-type mice by injecting an oxytocin receptor antagonist 1-1.5 hours after birth.
“Male and female mice with a genetic disruption that models Prader–Willi syndrome usually exhibit a lethal feeding deficiency. This feeding deficiency can be rescued with an injection of Oxt on PND0, or induced in wild-type mice by injecting an OTA 1–1.5 h after birth (64).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [64] Schaller, 2010, A single postnatal injection of oxytocin rescues the lethal feeding behaviour in mouse newborns deficient for the imprinted Magel2 gene, Hum Mol Genet source
It may state two separate claims as one.
InterpretationreasoningOxytocin in early postnatal development and during puberty can result in long-lasting changes in behavior, including affiliative and sexual behaviors as well as non-social behaviors such as nociception and ethanol consumption.
“It is apparent that Oxt in early postnatal development and during puberty can result in long-lasting changes in behavior, including behaviors that have traditionally been associated with Oxt’s acute neuromodulatory effects, such as affiliative and sexual behaviors, as well as non-social behaviors, such as nociception and ethanol consumption.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationIn females, a single injection of an oxytocin receptor antagonist on postnatal day 1 decreases expression of estrogen receptor alpha in the medial preoptic area of adult female prairie voles, increases estrogen receptor alpha expression in the BNST, and possibly decreases expression in the medial amygdala.
“These results differ from reports in females where a single injection of an OTA on PND1 decreases expression of ERα in the medial preoptic area (MPOA) of adult female prairie voles, as well as increases ERα expression in the BNST, and possibly decreases expression in the medial amygdala (MeA) (26)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Yamamoto, 2006, Neonatal manipulation of oxytocin affects expression of estrogen receptor alpha, Neuroscience source
It may state two separate claims as one.
PremisecitationIn male prairie voles, oxytocin has no effect on oxytocin immunoreactivity, but treatment with an oxytocin receptor antagonist decreases arginine vasopressin immunoreactivity in the paraventricular nucleus.
“Yet, in males, Oxt has no effect on Oxt-ir, but treatment with an OTA does decrease arginine vasopressin (Avp) immunoreactivity in the PVN (27).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [27] Yamamoto, 2004, Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner, Neuroscience source
It may state two separate claims as one.
PremisecitationNeonatal injections of oxytocin increase estrogen receptor alpha expression in the ventromedial hypothalamus of adult females, and oxytocin treatment on postnatal day 0 increases the number of estrogen receptor alpha-immunoreactive cells in the ventromedial hypothalamus of 3-week-old prairie voles.
“Neonatal injections of Oxt increase ERα expression in the ventromedial hypothalamus (VMH) of adult females and Oxt treatment on PND0 increases the number of ERα-immunoreactive (ERα-ir) cells in the VMH of 3-week-old prairie voles (26).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Yamamoto, 2006, Neonatal manipulation of oxytocin affects expression of estrogen receptor alpha, Neuroscience source
It may state two separate claims as one.
InterpretationreasoningOxytocin is able to acutely regulate stress responses but appears to also be involved in the development of long-term responsiveness to stress.
“So, not only is Oxt able to acutely regulate stress responses (81, 82) but appears to also be involved in the development of long-term responsiveness to stress.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [81] Windle, 1997, Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats 1, Endocrinology source
- cites [82] Neumann, 2000, Brain oxytocin inhibits basal and stress-induced activity of the hypothalamo-pituitary-adrenal axis in male and female rats: partial action within the paraventricular nucleus, J Neuroendocrinol source
It may state two separate claims as one.
InterpretationcitationDevelopmental oxytocin exposure affects many different neural circuits, and these effects can be highly dependent on the state of the dam.
“Thus, not only does developmental Oxt exposure affect many different neural circuits, these effects can also be highly dependent on the state of the dam.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationNeonatal oxytocin administration decreases dopamine turnover in the hypothalamus and serotonin turnover in the hypothalamus, medulla oblongata, and striatum of 4-month-old female rats.
“as well as decreases dopamine turnover in the hypothalamus as well as serotonin turnover in the hypothalamus, medulla oblongata, and striatum of 4-month-old female rats (84).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [84] Hashemi, 2013, Effect of a single neonatal oxytocin treatment (hormonal imprinting) on the biogenic amine level of the adult rat brain could oxytocin-induced labor cause pervasive developmental diseases?, Reprod Sci source
It may state two separate claims as one.
PremisecitationIn neonatal pigs, repeated oxytocin treatment increases adrenocorticotropic hormone at 8 weeks of age and decreases responsiveness in the dexamethasone suppression test at 11 weeks, indicative of dysregulation of the glucocorticoid response.
“In neonatal pigs, repeated Oxt treatment increases adrenocorticotropic hormone (ACTH) at 8 weeks of age and decreases responsiveness in the dexamethasone suppression test at 11 weeks; indicative of dysregulation of the glucocorticoid response.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [39] Rault, 2013, Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior, Physiol Behav source
It may state two separate claims as one.
PremisecitationPeripubertal oxytocin administration increases oxytocin receptor mRNA expression in the hypothalamus and plasma oxytocin levels in adult male rats.
“Similar to what was discussed in terms of behavioral effects, there does appear to be a “critical period” of organization that extends into peripubertal development, with peripubertal Oxt administration increasing Oxtr mRNA expression in the hypothalamus (41) and plasma Oxt levels (42) in adult male rats.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [41] Bowen, 2011, Adolescent oxytocin exposure causes persistent reductions in anxiety and alcohol consumption and enhances sociability in rats, PLoS One source
- cites [42] Suraev, 2014, Adolescent exposure to oxytocin, but not the selective oxytocin receptor agonist TGOT, increases social behavior and plasma oxytocin in adulthood, Horm Behav source
It may state two separate claims as one.
PremisecitationIn rats, chronic neonatal oxytocin treatment alters alpha-2 adrenergic receptor kinetics in postnatal day 130 male rats, and these changes are dependent upon the nutrition of the dam.
“In rats, chronic neonatal Oxt treatment alters α2 adrenergic receptor (α2r) kinetics in PND130 male rats; these changes are dependent upon the nutrition of the dam to which the pups were born.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [83] DÃaz-Cabiale, 2004, Long-term modulation by postnatal oxytocin of the α2-adrenoceptor agonist binding sites in central autonomic regions and the role of prenatal stress, J Neuroendocrinol source
Probably not a substantial claim.
Interpretationnone givenAn area that remains largely unexplored is the potential for oxytocin to have organizational effects during embryonic development.
“While research into the neonatal and peripubertal developmental effects of Oxt has been ever increasing, an area that remains largely unexplored is the potential for Oxt to have organizational effects during embryonic development.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationMany of the affected brain nuclei are part of the social behavioral network, which is comprised of interconnected nodes that express gonadal hormone receptors, appear to be influenced by oxytocin, and are important in the regulation of many types of social behaviors.
“What is particularly interesting about the aforementioned brain nuclei is that many of them are a part of the “social behavioral network,” which is comprised of neuroanatomical areas or “nodes” that are interconnected, express gonadal hormone receptors, appear to be influenced by Oxt, and are important in the regulation of many types of social behaviors (92, 93).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [92] Newman, 1999, The medial extended amygdala in male reproductive behavior. A node in the mammalian social behavior network, Ann N Y Acad Sci source
- cites [93] Albers, 2015, Species, sex and individual differences in the vasotocin/vasopressin system: relationship to neurochemical signaling in the social behavior neural network, Front Neuroendocrinol source
It may state two separate claims as one.
PremisecitationOxytocin or the oxytocin receptor is expressed in some of the brain regions affected by developmental oxytocin exposure, though their expression often varies depending on species, age, and sex.
“Oxt or the Oxtr is expressed in some of these regions (68, 91), though their expression in these brain areas often varies depending on species, age, and sex.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
InterpretationreasoningThere is still much we do not understand about the Oxt system, and filling this knowledge gap becomes more vital as the interest in using Oxt in clinical settings continues to increase.
“However, there is still much we do not understand about the Oxt system, and filling this “knowledge gap” becomes more vital as the interest in using Oxt in clinical settings continues to increase.”
Quote in the paperNot a substantial claim- Rests on an assumption: Intranasal Oxt has been marketed as the “cuddle” or “love” hormone, and is being used in a variety of contexts as a therapeutic agent to promote prosocial behaviors in humans.
Probably not a substantial claim. The paper may give no reason why it holds. It may state two separate claims as one.
Interpretationnone givenMuch of the work on intranasal Oxt has been performed in the absence of dose response studies, without serious consideration of the potential developmental or long-term effects, and with little attention paid to where in the brain these effects might be mediated.
“Much of this work has been performed in the absence of dose response studies, without serious consideration of the potential developmental or long-term effects, and with little attention paid to where in the brain these effects might be mediated.”
Quote in the paperNot a substantial claim- Rests on an assumption: Intranasal Oxt has been marketed as the “cuddle” or “love” hormone, and is being used in a variety of contexts as a therapeutic agent to promote prosocial behaviors in humans.
It may state two separate claims as one.
PremisecitationPrairie voles have a postnatal increase in Oxt peptide expression, with the number of Oxt expressing neurons significantly increasing from PND1 to PND21 in both males and females.
“Prairie voles also have a postnatal increase in Oxt peptide expression, with the number of Oxt expressing neurons significantly increasing from PND1 to PND21 in both males and females (27).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [27] Yamamoto, 2004, Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner, Neuroscience source
Probably not a substantial claim. The paper may give no reason why it holds.
InterpretationreasoningThe critical window for the manipulation of the Oxt system is plausibly not the same in males as in females, since there could be sex differences in its development.
“It is plausible that the “critical window” for the manipulation of the Oxt system is not the same in males as in females, since there could be sex differences in its development.”
Quote in the paperNot a substantial claimIt may state two separate claims as one.
InterpretationreasoningOxt signaling via the Oxtr during fetal development might be important for displays of aggressive behavior, and perhaps other behaviors in adulthood.
“These data suggest that Oxt signaling via the Oxtr during fetal development might be important for displays of aggressive behavior, and perhaps other behaviors in adulthood.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
PremisecitationMore recent studies in humans suggest that Oxt's effects are nuanced and that intranasal Oxt treatment can have undesirable effects.
“Thus, it is perhaps not surprising that more recent studies in humans suggest that Oxt’s effects are nuanced (as the data from animal models would suggest) and that intranasal Oxt treatment can have undesirable effects (106–108).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [106] Cardoso, 2014, The effect of intranasal oxytocin on perceiving and understanding emotion on the Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT), Emotion source
- cites [107] Ellenbogen, 2013, Intranasal oxytocin impedes the ability to ignore task-irrelevant facial expressions of sadness in students with depressive symptoms, Psychoneuroendocrinology source
- cites [108] Bartz, 2011, Oxytocin can hinder trust and cooperation in borderline personality disorder, Soc Cogn Affect Neurosci source
It may state two separate claims as one.
PremisecitationIn rats, Oxt mRNA is observed as early as E15.5 in the PVN and E18.5 in the SON.
“In rats, Oxt mRNA is observed as early as embryonic day (E) 15.5 in the PVN and E18.5 in the SON (103).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [103] Jing, 1998, Ontogeny of the vasopressin and oxytocin RNAs in the mouse hypothalamus, Neurosci Res source
Probably not a substantial claim. It may be too vague to check against evidence. It may state two separate claims as one.
Interpretationnone givenResearch into the role of Oxt in development is still in its early stages and there is much to do before we have a handle on its effects on the brain and behavior.
“Compared to what we understand about Oxt in adulthood, research into its role in development is still in its early stages and there is much to do before we really have a handle on its effects on the brain and behavior.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The heightened aggressive behavior phenotype is not observed when male mice are born to heterozygous dams.
“While this phenotype cannot be rescued if the pups are cross-fostered to wild-type dams (99), it is not observed when male mice are born to heterozygous dams.”
The paper relies on this without support.
Intranasal Oxt has been marketed as the “cuddle” or “love” hormone, and is being used in a variety of contexts as a therapeutic agent to promote prosocial behaviors in humans.
“For the last several years, intranasal Oxt has been marketed as the “cuddle” or “love” hormone, and is being used in a variety of contexts as a therapeutic agent to promote prosocial behaviors in humans.”
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 has been shown to influence brain and behavior differently at different developmental stages.
“Since oxytocin has been shown to influence brain and behavior differently at different developmental stages94, oxytocin efficacy might differ between adults and adolescents.”
From Randomized clinical trial shows no substantial modulation of empathy-related neural activation by intranasal oxytocin in autism (2021) · cites this paper as [94]
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.
Male mating outcome claimed despite no male data in table
MinorThe text attributes decreased mating-bout frequency to both sexes in study (20), while both Table 1 rows for that study list no male data.
“an injection of both Oxt and an Oxt receptor antagonist (OTA), also on PND1, decreases the frequency of mating bouts in both adult males and females (20).”
“| Prairie vole | 3.0 μg Oxt i.p. | PND0 | PND75 | ↓ Mating bout frequency | ND | (20) | | Prairie vole | 0.3 μg OTA i.p. | PND0 | PND75 | ↓ Mating bout frequency, ↑ litter production success | ND | (20) |”
Pig treatment age conflicts with Table 1
MinorThe text says pigs received intranasal oxytocin at 2.5-8 weeks of age, but Table 1 lists treatment on postnatal days 1-3 and assays at 2-8 weeks.
“Postnatal intranasal Oxt administration in 2.5- to 8-week-old pigs (Sus scrofa) increases intrasexual aggressive behavior and decreases social contact (39)”
“| Pig | 50.0 μg Oxt intranasally | PND1–3 | 2–8 weeks | ↑ Aggression | ↑ Aggression | (39) |”
Citations
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“Specifically, male Oxt−/− mice that are born to null mutant dams show heightened aggressive behavior in adulthood (97, 98).”
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Developmental effects of oxytocin neurons on social affiliation and processing of social information
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Metadata
- Authors
- Miller, T. V., & Caldwell, H. K.
- Affiliations
- Kent State University (US)
- Corresponding author
- Caldwell, Heather K.
- ORCID
- Caldwell, Heather K.
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2015-05-19
- Volume
- 6
- Pages
- 76-76
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC4437049
- OpenAlex
- W1498621943
- Semantic Scholar
- 5ccb6a1cfa3f5e1de6b8090420523170ce3477b2
- Cited by
- 79
- References
- 109
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 6 · 2023: 2 · 2022: 7 · 2021: 9 · 2020: 11 · 2019: 12 · 2018: 6 · 2017: 10 · 2016: 7 · 2015: 1
- FWCI
- 1.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (IOS353859)
- Kent State University
- Directorate for Biological Sciences
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- oxytocin, developmental programming, organizational effects, social behavior, affiliative behavior, parental behavior, aggression, postnatal development, peripubertal development, prenatal exposure, neural correlates, neurochemistry, neuroendocrinology
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.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
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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