Sex-specific effects of neonatal progestin receptor antagonism on juvenile social play behavior in rats
Open accessAbstract
Developing mammals are exposed to progesterone through several sources; however, the role of progesterone in early development is not well understood. Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life, suggesting that PRs may be important for the organization of the sex differences in the brain and behavior. Indeed, previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist. In the present study, we examined the role of PRs in organizing juvenile behaviors. Social play behavior and social discrimination were examined in juvenile male and female rats that had been treated with CDB, a PR antagonist, during the first week of postnatal life. Interestingly, neonatal PR antagonism altered different juvenile behaviors in males and females. A transient disruption in PR signaling during development had no effect on social discrimination but increased play initiation and pins in females. These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.
AI snapshot
Written from the paper’s full text.
TL;DR
Neonatal progestin receptor antagonism with CDB-4124 altered juvenile social play in a sex-specific manner, increasing play initiation and pins in female rats but not males. Social discrimination was unaffected.
Key findings
- CDB-treated females showed more pins than oil-treated females (simple main effect p = 0.02; table: 4.5 ± 0.9 vs 2.2 ± 0.5), while CDB had no effect in males (p = 0.93; 4.9 ± 0.6 vs 4.8 ± 0.7).
- Play initiation showed a sex × treatment interaction that approached significance (F(1,47) = 3.9, p = 0.05, η² = 0.08); the simple main effect of CDB in females approached significance (p = 0.06; table: 11.8 ± 1.6 vs 7.9 ± 1.5), with no effect in males (p = 0.37; 11.5 ± 1.2 vs 13.3 ± 1.7).
- No effects of sex or treatment were found on pounces or chases; bites were observed only several times total and were not analyzed independently.
- Social discrimination was not affected: no sex or treatment effects on percent novel anogenital investigations (sex p = 0.50; treatment p = 0.12) or body investigations (sex p = 0.42; treatment p = 0.75).
Methods
- Sprague–Dawley rats: 27 male and 25 female pups pooled from five litters, randomly assigned to CDB-4124 or vehicle and treated subcutaneously on PN0, PN2, and PN4. Final play analysis n: 12 CDB females, 11 oil females, 12 CDB males, 11 oil males; social discrimination n: 13 CDB females, 12 oil females, 13 CDB males, 14 oil males.
- Social play was recorded in the home cage on PN25–29: two 4-min sessions/day (8 min/day, 40 min total), scored for pin, pounce, bite, and chase by a blind observer. Social discrimination was tested on PN33 or PN34 after 4 h isolation: 5-min investigation of a stimulus rat, 30-min interval, then 5-min with familiar and novel stimulus rats; body and anogenital investigations were scored as percent novel.
- Two-way ANOVA with simple main effects; partial eta squared was used for effect size.
Limitations
- Stated: the mechanism for increased play in females is unclear, little is known about PRs in the developing postnatal female brain, and further studies are necessary.
- Stated: social discrimination is complex and other signaling molecules (e.g., oxytocin, vasopressin) are involved, so the lack of effect does not fully resolve PR’s role.
- Evident from the text: small group sizes (about 11–14 per group), a single CDB-4124 dose/regimen, no direct verification of PR antagonism, and no adult behavioral follow-up; one play cage was excluded because it contained animals of two different ages.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
13 of 37 cited sources checked · 7 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Males express more PRs than females within several hypothalamic regions on postnatal day 1 but not PN10.
“express more PRs than females within several hypothalamic regions on postnatal day (PN)1 but not PN10 [8, 9].”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [8] Quadros PS, Pfau JL, Goldstein AYN, De Vries GJ, Wagner CK. Sex differences in progesterone receptor expression: a potential mechanism for estradiol-mediated sexual differentiation. Endocrinology. 2002;143(10):3727–39. source
- cites [9] Wagner CK, Nakayama AY, De Vries GJ. Potential role of maternal progesterone in the sexual differentiation of the brain. Endocrinology. 1998;139(8):3658–61. source
The Results (p. 2) report significantly more PR-immunoreactive cells in males than females on the day of birth, but establish that difference only for the medial preoptic nucleus. The paper lists other regions containing PR-immunoreactive cells without reporting the same sex difference in them, and it does not report a PN10 comparison. (LLM, conf=0.88)
Experimental — accuracy not yet measured
- Premisecitation
Neonatal PR antagonism using RU-486 disrupts cognitive ability in adult male rats.
“Neonatal PR antagonism using RU-486 also disrupts cognitive ability in adult male rats [12].”
- Also stated in: § Abstract · plain
“previous studies showed cognitive impairments in male rats treated neonatally with a PR antagonist.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [12] Willing J, Wagner CK. Progesterone receptor expression in the developing mesocortical dopamine pathway: importance for complex cognitive behavior in adulthood. NEN. 2016;103(3–4):207–22. source
- Also stated in: § Abstract · plain
- Premiseown data
The present study is the first to show effects on juvenile social play behavior following a transient neonatal manipulation of PRs.
“Although previous data have demonstrated that PRs regulate social behavior in adults [17, 25], the present study is the first to show effects on juvenile social play behavior following a transient neonatal manipulation of PRs.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [17] Bychowski ME, Auger CJ. Progesterone impairs social recognition in male rats. Horm Behav. 2012;61(4):598–604. source
- cites [25] Bychowski ME, Mena JD, Auger CJ. Vasopressin infusion into the lateral septum of adult male rats rescues progesterone induced impairment in social recognition. Neuroscience. 2013;29:52–8. source
The Introduction and Discussion (pages unavailable) report that progesterone treatment impairs social recognition in adult male rats, supporting the cited sentence’s point about adult social behavior. The paper notes that relevant vasopressin cells contain progestin receptors, but it does not establish that the receptors themselves regulate that behavior. The claim about neonatal manipulation and juvenile play describes the citing authors’ present study, not this source. (LLM, conf=0.82)
Experimental — accuracy not yet measured
- Findingown data
The interaction between sex and treatment on initiation of play behavior approached significance.
“however, the interaction between sex approached significance [F(1,47) = 3.9, p = 0.05, Ŋ2 = 0.08, Fig. 2A].”
Quote in the paperNot a substantial claim - Findingown data
A transient disruption in PR signaling during development increased play initiation and pins in females.
“but increased play initiation and pins in females.”
- Also stated in: § Discussion · hedged
“neonatal PR antagonism increased play initiation and pins in females, with no effect in males.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · hedged
- Findingown data
There was no main effect of sex on initiation of play behavior.
“There was no main effect of sex [F(1,47) = 3.1, p = 0.09, Ŋ2 = 0.07] or treatment F(1,47) = 0.52, p = 0.48, Ŋ2 = 0.01 on the initiation of play behavior”
Quote in the paperNot a substantial claim - Findingown data
A transient disruption in PR signaling during development had no effect on social discrimination.
“A transient disruption in PR signaling during development had no effect on social discrimination”
- Also stated in: § Discussion · plain
“there was no effect on social discrimination following neonatal PR antagonism.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
There was no main effect of treatment on initiation of play behavior.
“There was no main effect of sex [F(1,47) = 3.1, p = 0.09, Ŋ2 = 0.07] or treatment F(1,47) = 0.52, p = 0.48, Ŋ2 = 0.01 on the initiation of play behavior”
Quote in the paperNot a substantial claim - Findingown data
The interaction between sex and treatment on pins approached significance.
“while the main effect of treatment [F(1,47) = 3.3; p = 0.08, Ŋ2 = 0.07] and interaction between sex and treatment [F(1,47) = 2.8, p = 0.09, Ŋ2 = 0.06] approached significance”
Quote in the paperNot a substantial claim - Findingown data
There was a main effect of sex on pins.
“There was a main effect of sex [F(1,47) = 5.4; p = 0.03, Ŋ2 = 0.11] on pins”
Quote in the paperSubstantial claim - Findingown data
CDB-treated females pinned more than control females.
“Simple main effects indicate CDB-treated females pinned more than control females (p = 0.02)”
Quote in the paperSubstantial claim - Findingown data
The effect of CDB on play initiation in females approached significance.
“Simple main effects indicate that the effect of CDB in females approached significance (p = 0.06)”
Quote in the paperNot a substantial claim - Findingown data
The main effect of treatment on pins approached significance.
“while the main effect of treatment [F(1,47) = 3.3; p = 0.08, Ŋ2 = 0.07] and interaction between sex and treatment [F(1,47) = 2.8, p = 0.09, Ŋ2 = 0.06] approached significance”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of CDB on play initiation in males.
“while there was no effect of CDB in males (p = 0.37).”
Quote in the paperSubstantial claim - Findingown data
Males initiated play more than females.
“males initiated play more than females and exhibited more pins”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of sex on percent novel body investigations.
“and no effect of sex [F(1,50) = 0.36; p = 0.42] or treatment [F(1,50) = 1.1; p = 0.75] on percent novel body investigations (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of sex on percent novel anogenital investigations.
“There was no effect of sex [F(1,50) = 0.47; p = 0.50] or treatment [F(1,50) = 2.5; p = 0.12] on percent novel anogenital investigations (Fig. 3A)”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of CDB on pins in males.
“while there was no effect of CDB in males (p = 0.93).”
Quote in the paperSubstantial claim - Findingown data
Males exhibited more pins than females.
“males initiated play more than females and exhibited more pins”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of treatment on percent novel body investigations.
“and no effect of sex [F(1,50) = 0.36; p = 0.42] or treatment [F(1,50) = 1.1; p = 0.75] on percent novel body investigations (Fig. 3B).”
Quote in the paperNot a substantial claim - Findingown data
There was no effect of treatment on percent novel anogenital investigations.
“There was no effect of sex [F(1,50) = 0.47; p = 0.50] or treatment [F(1,50) = 2.5; p = 0.12] on percent novel anogenital investigations (Fig. 3A)”
Quote in the paperNot a substantial claim - Premisecitation
Males express PRs as early as embryonic day 20 in many brain areas.
“Males express PRs as early as embryonic day 20 in many brain areas [7]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [7] Quadros PS, Pfau JL, Wagner CK. Distribution of progesterone receptor immunoreactivity in the fetal and neonatal rat forebrain. J Comp Neurol. 2007;504(1):42–56. source
- Premisecitation
Male and female rodents have approximately equivalent levels of circulating progesterone during development.
“Indeed, male and female rodents have approximately equivalent levels of circulating progesterone during development [4, 5].”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [4] Nguyen PN, Billiards SS, Walker DW, Hirst JJ. Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in the perinatal sheep. Pediatr Res. 2003;53(6):956–64. source
- cites [5] Weisz J, Ward IL. Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring. Endocrinology. 1980;106(1):306–16. source
- Interpretationreasoning
The sex difference in PRs in the developing brain suggests that PRs are important for the organization of sex differences in the brain.
“This sex difference in PRs in the developing brain suggests that PRs are important for the organization of the sex differences in the brain.”
Quote in the paperSubstantial claim - Premisenone given
Males express more PRs than females within several brain regions during early postnatal life.
“Males express more progestin receptors (PRs) than females within several brain regions during early postnatal life”
Quote in the paperNot a substantial claim - Interpretationown data
These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.
“These data suggest that PRs play an important role in the organization of sex differences in some social behaviors.”
Quote in the paperSubstantial claim - Interpretationown data
PR signaling may play a role in organizing female social play behavior.
“PR signaling may play a role in organizing female social play behavior.”
Quote in the paperSubstantial claim - Interpretationown data
The present data suggest that PRs do not play an organizational role in social discrimination during the first week of postnatal life.
“the present data suggest that PRs do not play an organizational role in this behavior during the first week of postnatal life.”
Quote in the paperSubstantial claim - Interpretationreasoning
The increase in play initiation in CDB-treated females is driven primarily by increases in pins.
“suggesting that the increase in play initiation in CDB-treated females is driven primarily by increases in pins.”
Quote in the paperSubstantial claim - Interpretationreasoning
During the first week of postnatal life, PRs appear to be important for establishing female-typical levels of play.
“during the first week of postnatal life, PRs appear to be important for establishing female-typical levels of play.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 23
- May combine two claims. 10
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationCDB-4124 has been shown to affect forced swim immobility in adult mice.
“that has been shown to affect forced swim immobility in adult mice [14].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [14] Beckley EH, Scibelli AC, Finn DA. Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability. Psychoneuroendocrinology. 2011;36(6):824–33. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationProgesterone administration disrupts social recognition in adult males.
“progesterone administration has been found to disrupt social recognition in adult males [17]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [17] Bychowski ME, Auger CJ. Progesterone impairs social recognition in male rats. Horm Behav. 2012;61(4):598–604. source
The Discussion reports that progesterone interferes with social recognition memory in adult male rats. The citing sentence omits the species, so the result does not establish the effect in adult males generally. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationAnother study using ZK 137616 found no effect on male mouse sex behavior.
“another study using a different PR antagonist, ZK 137616, found no effect on male mouse sex behavior [11].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [11] Desroziers E, Brock O, Bakker J. Potential contribution of progesterone receptors to the development of sexual behavior in male and female mice. Horm Behav. 2017;1(90):31–8. source
The Methods section identifies the antagonist as ZK137316, not ZK 137616. The male sexual behavior Results report no difference in the numbers of mounts, intromissions, or ejaculations, but significantly shorter latencies for all three in the first mating test; therefore, 'no effect' overstates the finding. Page numbers are unavailable in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measured
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationSocial discrimination is a complex behavior, and several other signaling molecules have been shown to play a role in social discrimination, including oxytocin and arginine vasopressin.
“social discrimination is a complex behavior, and several other signaling molecules have been shown to play a role in social discrimination, including oxytocin [35–37] and arginine vasopressin [24, 38–40].”
Quote in the paperNot a substantial claim1 of 7 sources checked- cites [35] Engelmann M, Ebner K, Wotjak CT, Landgraf R. Endogenous oxytocin is involved in short-term olfactory memory in female rats. Behav Brain Res. 1998;90(1):89–94. source
- cites [36] Ferguson JN, Aldag JM, Insel TR, Young LJ. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J Neurosci. 2001;21(20):8278–85. source
- cites [37] Ferguson JN, Young LJ, Hearn EF, Matzuk MM, Insel TR, Winslow JT. Social amnesia in mice lacking the oxytocin gene. Nat Genet. 2000;25(3):284–8. source
- cites [24] Bielsky IF, Hu S-B, Ren X, Terwilliger EF, Young LJ. The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron. 2005;47(4):503–13. source
- cites [38] Bluthe RM, Schoenen J, Dantzer R. Androgen-dependent vasopressinergic neurons are involved in social recognition in rats. Brain Res. 1990;519(1–2):150–7. source
- cites [39] Bluthé RM, Gheusi G, Dantzer R. Gonadal steroids influence the involvement of arginine vasopressin in social recognition in mice. Psychoneuroendocrinology. 1993;18(4):323–35. source
- cites [40] Dantzer R, Koob GF, Bluthé R-M, le Moal M. Septal vasopressin modulates social memory in male rats. Brain Res. 1988;457(1):143–7. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPrior studies have found an increase in arginine vasopressin expression in the lateral habenula of PR knockout mice.
“Prior studies have found an increase in arginine vasopressin expression in the lateral habenula of PR knockout mice [34]”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [34] Rood BD, Murray EK, Laroche J, Yang MK, Blaustein JD, De Vries GJ. Absence of progestin receptors alters distribution of vasopressin fibers but not sexual differentiation of vasopressin system in mice. Neuroscience. 2008;154(3):911–21. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationManipulation of PRs may affect a variety of signaling molecules, such as arginine vasopressin, opioids, endocannabinoids, dopamine, norepinephrine, serotonin, and GABA, which are all involved in social play behavior.
“Manipulation of PRs may affect a variety of signaling molecules, such as arginine vasopressin, opioids, endocannabinoids, dopamine, norepinephrine, serotonin, and GABA, which are all involved in social play behavior [31–33].”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [31] Auger AP, Olesen KM. Brain sex differences and the organization of juvenile social play behavior. J Neuroendocrinol. 2009;21(6):519–25. source
The 'Neurotransmitters and play development' section links dopamine and the opioid system to juvenile social play, and 'Social play and activity level' reports an effect of cannabinoid receptor agonists. But the 'Possible convergence of neurotransmitters and steroid receptors' section describes dopamine activating progestin receptors, not PR manipulation affecting the listed molecules. Our copy does not establish a role in social play for every molecule named in the claim. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [32] Trezza V, Baarendse PJJ, Vanderschuren LJMJ. The pleasures of play: pharmacological insights into social reward mechanisms. Trends Pharmacol Sci. 2010;31(10):463–9. source
The Introduction and the Dopamine section link opioids, endocannabinoids, dopamine, norepinephrine, serotonin, and GABA to social play; the References list a study of vasopressin and play fighting. However, the paper does not establish that manipulating PRs affects these signaling molecules. Page numbers were not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [33] Vanderschuren LJ, Niesink RJ, Van Ree JM. The neurobiology of social play behavior in rats. Neurosci Biobehav Rev. 1997;21(3):309–26. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThese results are consistent with a recent study demonstrating a sex difference in pins and total play, but not chases, in both mixed-sex and same-sex pairs.
“These results are also consistent with a recent study demonstrating a sex difference in pins and total play, but not chases, in both mixed-sex and same-sex pairs [30].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [30] Argue KJ, McCarthy MM. Characterization of juvenile play in rats: importance of sex of self and sex of partner. Biol Sex Differ. 2015;6(1):16. source
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationThe dose of CDB-4124 is within the range of what has previously had an effect on forced swim immobility in adult mice.
“The dose of CDB-4124 is within the range of what has previously had an effect on forced swim immobility in adult mice [14].”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [14] Beckley EH, Scibelli AC, Finn DA. Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability. Psychoneuroendocrinology. 2011;36(6):824–33. source
May combine two claims.
Findingown dataThere were no main effects or interactions on pounces or chases.
“There were no main effects or interactions on pounces or chases (Table 1).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn females, there was an increase in play initiation, while there was no effect in males.
“In females, there was an increase in play initiation, while there was no effect in males.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Findingnone givenEffect sizes for all reported statistics are in the medium-large range.
“Effect sizes for all reported statistics are in the medium-large range.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationProgestin antiserum decreased play only in females.
“progestin antiserum decreased play only in females [16].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] Birke LI, Sadler D. Modification of juvenile play and other social behaviour in the rat by neonatal progestins: further studies. Physiol Behav. 1984;33(2):217–9. source
Classified as probably not a substantial claim. May combine two claims.
PremisecitationBlocking PRs using RU-486 during development increases male sex behavior and AR expression in several regions of the adult male brain.
“blocking PRs using RU-486 during development increases male sex behavior and the expression of ARs in several regions of the adult male brain [10]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [10] Forbes-Lorman R, Auger AP, Auger CJ. Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats. Brain Res. 2014;16(1543):143–50. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationDeveloping mammals are exposed to progesterone from fetal and maternal sources.
“Developing mammals are exposed to progesterone, both from fetal and maternal sources (reviewed in [2, 3]).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [2] González-Orozco JC, Camacho-Arroyo I. Progesterone actions during central nervous system development. Front Neurosci. 2019. https://doi.org/10.3389/fnins.2019.00503/full. source
Not checked in the free run.
- cites [3] Morel Y, Roucher F, Plotton I, Goursaud C, Tardy V, Mallet D. Evolution of steroids during pregnancy: maternal, placental and fetal synthesis. Annales D’endocrinologie. 2016;77(2):82–9. source
May combine two claims.
PremisecitationCDB-4124 is a PR antagonist with low binding affinity for glucocorticoid receptors.
“CDB-4124 is a PR antagonist with a low binding affinity for glucocorticoid receptors [13]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [13] Attardi BJ, Burgenson J, Hild SA, Reel JR, Blye RP. CDB-4124 and its putative monodemethylated metabolite, CDB-4453, are potent antiprogestins with reduced antiglucocorticoid activity: in vitro comparison to mifepristone and CDB-2914. Mol Cell Endocrinol. 2002;188(1–2):111–23. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationNeonatal progesterone administration increased play in both sexes.
“neonatal progesterone administration increased play in both sexes [15]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [15] Birke LI, Sadler D. Progestin-induced changes in play behaviour of the prepubertal rat. Physiol Behav. 1983;30(3):341–7. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationA more recent study showed the opposite effect of progesterone on social recognition.
“while a more recent study showed the opposite [18].”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [18] Kavaliers M, Bishnoi IR, Ossenkopp K-P, Choleris E. Differential effects of progesterone on social recognition and the avoidance of pathogen threat by female mice. Horm Behav. 2021;127: 104873. source
May combine two claims.
Study design and conductown dataSesame oil does not clear within a day, so treatment was likely continuous from approximately PN0 to PN6.
“We have found that the sesame oil does not clear within a day, so treatment was likely continuous from ~ PN0-PN6.”
Quote in the paperNot a substantial claim- Rests on an assumption: Sesame oil does not clear within a day.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductcitationThe animals from one cage were not used in the final analysis because this cage contained animals of two different ages and social play changes with age.
“The animals from one cage were not used in the final analysis because this cage contained animals of two different ages and social play changes with age [22, 23].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [22] Pellis SM, Pellis VC. Differential rates of attack, defense, and counterattack during the developmental decrease in play fighting by male and female rats. Dev Psychobiol. 1990;23(3):215–31. source
- cites [23] Thor DH, Holloway WR. Social play in juvenile rats: a decade of methodological and experimental research. Neurosci Biobehav Rev. 1984;8(4):455–64. source
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe treatment regimen is similar to what has been previously used for RU-486.
“This treatment regimen is similar to what has been previously used for RU-486 [10]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] Forbes-Lorman R, Auger AP, Auger CJ. Neonatal RU-486 (mifepristone) exposure increases androgen receptor immunoreactivity and sexual behavior in male rats. Brain Res. 2014;16(1543):143–50. source
Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).
Premisenone givenThe present study is the first to examine the specific role of PRs during early development on juvenile social behaviors.
“To my knowledge, the present study is the first to examine the specific role of PRs during early development on juvenile social behaviors.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenAn observer blind to the treatment groups scored the recordings for play behaviors.
“An observer blind to the treatment groups scored the recordings for the following individual behaviors: pin, pounce, bite, and chase.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenEach behavior was recorded and then analyzed by a trained technician blind to all treatments.
“Each behavior was recorded and then analyzed by a trained technician blind to all treatments using The Observer® (Noldus Information Technologies) or Stopwatch + (Center for Behavioral Neuroscience, Atlanta, GA).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationPinning may be indicative of dominance.
“pinning may be indicative of dominance [21, 29].”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [21] Argue KJ, McCarthy MM. Utilization of same- vs. mixed-sex dyads impacts the observation of sex differences in juvenile social play behavior. Curr Neurobiol. 2015;6(1):17–23.
Not checked in the free run.
- cites [29] Panksepp J. The ontogeny of play in rats. Dev Psychobiol. 1981;14(4):327–32. source
Classified as probably not a substantial claim. May combine two claims.
Study design and conductreasoningIn order to minimize litter effects, each cage contained 1-2 animals from each treatment group and approximately half females and half males.
“In order to minimize litter effects, each cage contained 1–2 animals from each treatment group (i.e., CDB-treated females, CDB-treated males, vehicle-treated females, vehicle-treated males) and approximately half females and half males.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
Study design and conductcitationJuvenile animals were isolated for only 4 h prior to social discrimination testing because social isolation is considered a severe stressor for juvenile animals.
“we isolated the juvenile animals for only 4 h in this study, as social isolation is considered a severe stressor for juvenile animals [26].”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [26] Mumtaz F, Khan MI, Zubair M, Dehpour AR. Neurobiology and consequences of social isolation stress in animal model—a comprehensive review. Biomed Pharmacother. 2018;105:1205–22. source
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenEach litter contained animals of both sexes and treatment groups, and a maximum of three animals from a single litter were assigned to each treatment group.
“Each litter contained animals of both sexes and treatment groups and a maximum of three animals from a single litter were assigned to each treatment group.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
RU-486 also binds glucocorticoid receptors.
“It should be noted that RU-498 also binds glucocorticoid receptors, making the role of PRs during development even less clear.”
The paper relies on this without support.
Sesame oil does not clear within a day.
“We have found that the sesame oil does not clear within a day”
Statistics that don’t add up
Each reported p-value recomputed from its test statistic and degrees of freedom.
Inconsistent p-value: F(1,47) = 2.8, p = .09
MinorThe paper reports p = .09 here; recomputing from the test statistic and its degrees of freedom gives p = .101. The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .09 · recomputed p = .101
“F(1,47) = 2.8, p = 0.09”
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Doesn’t add upF(1, 47) = 2.8reported p = .09 · recomputed p = .101
“F(1,47) = 2.8, p = .09”
- ConsistentF(1, 47) = 3.1reported p = .09 · recomputed p = .085
“F(1,47) = 3.1, p = .09”
- ConsistentF(1, 47) = 0.52reported p = .48 · recomputed p = .474
“F(1,47) = 0.52, p = .48”
- ConsistentF(1, 47) = 3.9reported p = .05 · recomputed p = .054
“F(1,47) = 3.9, p = .05”
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.
Not all reported effect sizes are medium or large
MinorThe paper defines a medium effect size as Ŋ2 = 0.06, yet reports an effect size of 0.01. Thus, its statement about all reported effect sizes is false.
“Effect sizes for all reported statistics are in the medium-large range.”
“or treatment F(1,47) = 0.52, p = 0.48, Ŋ2 = 0.01”
Social-discrimination ANOVA degrees of freedom do not match the sample
MinorThe four social-discrimination groups total 52 animals. Under the stated two-way ANOVA, the residual degrees of freedom would be 48 rather than 50.
“There was no effect of sex [F(1,50) = 0.47; p = 0.50] or treatment [F(1,50) = 2.5; p = 0.12] on percent novel anogenital investigations”
“Animal numbers for social discrimination were 13 CDB-treated females, 12 oil-treated females, 13 CDB-treated males, and 14 oil-treated males.”
Play-behavior ANOVA degrees of freedom exceed the reported sample
MinorThe four play-behavior groups total 46 animals. A two-way ANOVA with four groups would have 42 residual degrees of freedom, not the reported 47.
“There was no main effect of sex [F(1,47) = 3.1, p = 0.09, Ŋ2 = 0.07]”
“Animal numbers for play behavior were therefore 12 CDB-treated females, 11 oil-treated females, 12 CDB-treated males, and 11 oil-treated males).”
Social-discrimination F statistics and p-values run in opposite directions
MinorFor tests with the same degrees of freedom, a larger F statistic must have a smaller p-value. The reported F of 1.1 has p = 0.75, whereas the smaller F of 0.36 has p = 0.42.
“treatment [F(1,50) = 1.1; p = 0.75] on percent novel body investigations”
“sex [F(1,50) = 0.36; p = 0.42]”
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Self-citation
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Cited by
Sorted by citations
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- Authors
- Forbes-Lorman, R. M.
- ORCID
- Forbes-Lorman, R. M.
- Venue
- Behavioral and Brain Functions
- Published
- 2021-11-05
- Volume
- 17
- Issue
- 1
- Pages
- 10-10
- ISSN
- 1744-9081 (ISSN-L)
- PMC
- PMC8571883
- OpenAlex
- W3176295846
- Semantic Scholar
- 8a74f85980bbd2e23924f1331e9c5da37fce653d
- Cited by
- 1
- References
- 42
- Citations by year
- 2023: 1
- FWCI
- 0.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Behavioral and Brain Functions (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, other-oa)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Science Foundation (1122074)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Keywords
- progestin receptor, progesterone, neonatal hormone exposure, CDB, social discrimination, sex differences, sexual differentiation of the brain, play initiation, postnatal development
- MeSH terms
- Animals, Brain, Female, Male, Progesterone, Receptors, Progesterone, Sex Characteristics, Social Behavior, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.
Cited sources are checked by gpt-6-sol.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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