The DOI matches its Crossref record; 74 of the 74 references it cites were found in a registry or an index; 44 of the 76 sources its claims cite were checked for support.
Peripubertal stress increases play fighting at adolescence and modulates nucleus accumbens CB1 receptor expression and mitochondrial function in the amygdala
Open accessAbstract
Play fighting is a highly rewarding behavior that helps individuals to develop social skills. Early-life stress has been shown to alter play fighting in rats and hamsters as well as to increase aggressive behaviors at adulthood. However, it is not known whether individual differences in stress-induced play fighting are related to differential developmental trajectories towards adult aggression. To address this question, we used a rat model of peripubertal stress (PPS)-induced psychopathology that involves increased aggression at adulthood. We report that, indeed, PPS leads to enhanced play fighting at adolescence. Using a stratification approach, we identify individuals with heightened levels of play fighting as the ones that show abnormal forms of aggression at adulthood. These animals showed as well a rapid habituation of their corticosterone responsiveness to repeated stressor exposure at peripuberty. They also showed a striking increase in mitochondrial function in the amygdala—but not nucleus accumbens—when tested ex vivo. Conversely, low, but not high players, displayed increased expression of the CB1 cannabinoid receptor in the nucleus accumbens shell. Our results highlight adolescence as a potential critical period in which aberrant play fighting is linked to the emergence of adult aggression. They also point at brain energy metabolism during adolescence as a possible target to prevent adult aggression.
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Written from the paper’s full text.
TL;DR
Peripubertal stress (PPS) in male rats increased adolescent play fighting, and a stratification approach identified PPS high players as those showing abnormal adult aggression, blunted corticosterone responses to repeated peripubertal stress, and increased amygdala mitochondrial respiration. PPS also increased CB1 receptor expression in the nucleus accumbens shell, particularly in low players, while no such changes appeared in the basolateral amygdala or NAc core.
Key findings
- PPS rats showed higher play fighting than controls at P45 for the compound index (U = 252.00, p < 0.01) and for pinning (U = 269.50, p < 0.05), pouncing (U = 284.00, p < 0.05), boxing (U = 243.00, p < 0.01), and kicking (U = 247.50, p < 0.01); they also had shorter latency to play fight (U = 270.00, p < 0.05), with no group difference in social exploration (t56 = 1.19, n.s.).
- Stratified PPS high players showed higher play fighting than both controls and PPS low players (all p < 0.001); PPS high players had lower corticosterone than low players on P30 after the third stressor exposure (U = 0.00, p < 0.01), but not on P28 (U = 4.00, n.s.).
- At adulthood, PPS low players showed more attacks than controls (p < 0.05), whereas PPS high players showed increased frequency of abnormal attacks compared with controls (p < 0.05); both PPS groups showed reduced juvenile exploration and increased floating on day 2 of the forced-swim test.
- CB1 expression in the NAc shell was higher in PPS rats than controls (t20 = 3.27, p < 0.01), and PPS low players had higher CB1 expression than controls (p < 0.05), with no differences in BLA or NAc core. Amygdala mitochondrial respiration showed a main effect of stress (F(1,56) = 7.56, p < 0.01) but not in NAc (F(1,56) = 2.86, n.s.); PPS high players had higher amygdala respiration than controls and PPS low players (all p < 0.01), and play fighting percentage positively correlated with amygdala CI (r16 = 0.52, p < 0.05) and CI+II (r16 = 0.52, p < 0.05) respiration.
Methods
- Male Wistar Han rats were assigned to control or PPS; PPS consisted of fear-inducing stressors (fox odor TMT and/or elevated platform) on 7 non-consecutive days from P28 to P42. Play fighting was tested on P45 after 3.5 h social isolation in dyads, with behavior video-recorded and manually scored.
- Three experiments assessed: adult behavior (social preference, resident-intruder, forced-swim), gene expression 24 h after play fighting, and mitochondrial respiration directly after play fighting. Stratification classified rats as high or low players using extremes (20th or 80th percentile) of the control distribution across five play measures; three of five scores defined a high player.
- Analyses used t-tests, ANOVAs, repeated-measures ANOVAs, Kruskal–Wallis with Dunnett’s post hoc tests, and linear mixed models with block as a random effect for respiration; significance was set at p < 0.05.
Limitations
- Stated: the study focused on males only, while sex-specific mechanisms have been shown to regulate social play behavior.
- Stated: mitochondrial respiration was measured ex vivo with excess substrates, reflecting maximal capacity rather than necessarily in vivo function before sampling; CB1 mRNA measures the total pool and cell type cannot be identified, so effects on mitochondrial CB1 expression cannot be concluded.
- Evident: stratified molecular and respiration subgroups were very small (e.g., PPS low player n = 3 and PPS high player n = 5 for respiration; PPS high player n = 3 for CB1), and control high players numbered n = 2, precluding statistics and limiting power.
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Claims the paper makes
44 of 76 cited sources checked · 32 supported · 0 flagged · accuracy not yet measured
- Premisecitation
Social play is modulated by early life experiences.
“Importantly, social play has been shown to be modulated by early life experiences.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [8] Veenema, A. H. & Neumann, I. D. Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats. Psychoneuroendocrinology 34, 463–467 (2009). source
- cites [10] Varlinskaya, E. I., Truxell, E. M. & Spear, L. P. Repeated restraint stress alters sensitivity to the social consequences of ethanol differentially in early and late adolescent rats. Pharmacol. Biochem. Behav. 113, 38–45 (2013). source
- cites [11] Wall, V. L., Fischer, E. K. & Bland, S. T. Isolation rearing attenuates social interaction-induced expression of immediate early gene protein products in the medial prefrontal cortex of male and female rats. Physiol. Behav. 107, 440–450 (2012). source
- Premisecitation
The endocannabinoid system has a role in social functioning, including modulation of play fighting.
“Recent studies have emphasized a role for the endocannabinoid system in social functioning52 including the modulation of play fighting53.”
Quote in the paperSubstantial claim1 of 2 sources checked- cites [52] Karhson, D. S., Hardan, A. Y. & Parker, K. J. Endocannabinoid signaling in social functioning: an RDoC perspective. Transl. Psychiatry 6, e905 (2016). source
- cites [53] Trezza, V. & Vanderschuren, L. J. M. J. Bidirectional cannabinoid modulation of social behavior in adolescent rats. Psychopharmacol. (Berl.) 197, 217–227 (2008). source
- Premisecitation
Intra-BLA and intra-NAc infusions of an endocannabinoid agonist increase play fighting through actions on the CB1 receptor.
“Given that both, intra-BLA and intra-NAc infusions of an endocannabinoid agonist increase play fighting23,24 through actions on the CB1 receptor23,24,53, we assessed CB1 mRNA levels in these brain regions.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [23] Manduca, A. et al. Interacting cannabinoid and opioid receptors in the nucleus accumbens core control adolescent social play. Front. Behav. Neurosci. 10, 211 (2016). source
- cites [24] Trezza, V. et al. Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.J. Neurosci. Off. J. Soc. Neurosci. 32, 14899–14908 (2012). source
The Results (page not provided) report that URB597 infused into either the BLA or NAc increased pinning and pouncing, measures of play fighting. CB1 antagonist infusion into the BLA blocked the play-enhancing effect of systemic URB597, but antagonist infusion into the NAc did not. The source therefore supports the CB1 mechanism in the BLA, not the claim that it was established in both regions. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [53] Trezza, V. & Vanderschuren, L. J. M. J. Bidirectional cannabinoid modulation of social behavior in adolescent rats. Psychopharmacol. (Berl.) 197, 217–227 (2008). source
- Premisecitation
Substantial evidence supports the involvement of both NAc shell and core in play fighting.
“Substantial evidence supports the involvement of both NAc shell and core in play fighting.”
Quote in the paperNot a substantial claim4 of 4 sources checked- cites [54] van Kerkhof, L. W. M. et al. Cellular activation in limbic brain systems during social play behaviour in rats. Brain. Struct. Funct. 219, 1181–1211 (2014). source
- cites [55] van Kerkhof, L. W., Damsteegt, R., Trezza, V., Voorn, P. & Vanderschuren, L. J. Social play behavior in adolescent rats is mediated by functional activity in medial prefrontal cortex and striatum. Neuropsychopharmacology 38, 1899–1909 (2013). source
In 'Inactivation of the NAcc Core Enhances the Duration of Social Play Behavior,' the paper reports that core inactivation prolonged social play and that play was associated with increased activity in both the core and shell. But the same section says the shell experiments were confounded by feeding and that its involvement in social play remains difficult to establish. Thus, 'substantial evidence' for involvement of both regions overstates the evidence for the shell. (LLM, conf=0.86)
Experimental — accuracy not yet measured - cites [19] Trezza, V., Damsteegt, R., Achterberg, E. J. M. & Vanderschuren, L. J. M. J. Nucleus accumbens μ-opioid receptors mediate social reward. J. Neurosci. 31, 6362–6370 (2011). source
- cites [56] Manduca, A. et al. Dopaminergic neurotransmission in the nucleus accumbens modulates social play behavior in rats. Neuropsychopharmacology 41, 2215–2223 (2016). source
- Study design and conductcitation
An important limitation of the study is that it focused on males, while sex-specific mechanisms have been shown to regulate social play behavior.
“We should also note that an important limitation of our study is that we focused in males, while sex-specific mechanisms have been shown to regulate social play behavior71.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [71] Bredewold, R., Smith, C. J. W., Dumais, K. M. & Veenema, A. H. Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context. Front. Behav. Neurosci. 8, 216 (2014). source
- Findingown data
Both PPS low and PPS high players show higher floating time than controls on the second day of the forced-swim test at adulthood.
“Both PPS low and high players showed higher floating time than CTRLs (p < 0.05).”
Quote in the paperNot a substantial claim - Findingown data
There is no evidence for differential regulation of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) gene expression in the brain regions of interest after PPS.
“Finally, given that PPS high and low player groups differed in their regulation of corticosterone responses to stress, we assessed expression levels of the glucocorticoid (GR) and mineralocorticoid receptor (MR) in the brain regions of interest, but found no evidence for a differential regulation of these genes (Figure S8).”
Quote in the paperNot a substantial claim - Findingown data
PPS high players show an increased frequency of abnormal attacks compared to control rats at adulthood.
“However, PPS high player animals showed increased frequency of abnormal attacks compared to CTRLs (Fig. 1m; H(3) = 6.06, p < 0.05; post hoc analyses p < 0.05).”
Quote in the paperSubstantial claim - Findingown data
Only PPS individuals with particularly heightened levels of play fighting show abnormal forms of aggression.
“although both peripubertally stressed groups show reduced sociability and increased passive coping responses at adulthood, only those individuals with particularly heightened levels of play fighting are the ones that show abnormal forms of aggression.”
Quote in the paperSubstantial claim - Findingown data
There are no significant differences in mitochondrial respiration in the nucleus accumbens according to play fighting stratification.
“No significant differences in the mitochondrial respiration in the NAc were found according to this analysis (Fig. 3g).”
Quote in the paperNot a substantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
- Findingown data
When control data are stratified by high and low players, no differences in mitochondrial function are observed in the amygdala or nucleus accumbens.
“When data from controls was analyzed according to the same stratification based on high and low players, no differences in mitochondrial function were observed in the amygdala or the nucleus accumbens [Figure S2e,f; but note that statistics are not possible due to the low number (n = 2) of high players in CTRL animals].”
Quote in the paperNot a substantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
- Findingown data
Play fighting was increased in PPS rats compared to CTRLs.
“Play fighting was increased in PPS rats compared to CTRLs (b).”
Quote in the paperSubstantial claim - Findingown data
No significant change was observed in mitochondrial respiration in the nucleus accumbens (NAc).
“No significant change was observed in the mitochondrial respiration in the nucleus accumbens (NAc) (d).”
Quote in the paperNot a substantial claim - Findingown data
Both peripubertally stressed groups (high and low play fighting) show reduced sociability at adulthood.
“although both peripubertally stressed groups show reduced sociability and increased passive coping responses at adulthood, only those individuals with particularly heightened levels of play fighting are the ones that show abnormal forms of aggression.”
Quote in the paperNot a substantial claim - Findingown data
In adult rats submitted to PPS and classified by adolescent play fighting levels, CB1 expression in the nucleus accumbens core is significantly lower in PPS low players than in PPS high players.
“While we did not find differences in the amygdala or in the NAc shell, CB1 expression levels in the NAc core were significantly lower in PPS low than in high players (Figure S5).”
Quote in the paperSubstantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
Both PPS high and PPS low players exhibit decreased exploration of a juvenile in the social preference test at adulthood compared to controls.
“In the social preference test, PPS induced a decrease in the exploration of the juvenile as compared to CTRLs (Fig. 1k; H(3) = 16.20, p < 0.001). However, both PPS low (p < 0.05) and high player (p < 0.001) groups exhibited reduced exploration but did not differ between themselves.”
Quote in the paperNot a substantial claim - Findingown data
Play fighting percentage positively correlates with complex I- and complex I+II-dependent respiration in the amygdala.
“Interestingly, we found significant positive correlations between play fighting percentage and respiration in amygdala (CI: r16 = 0.52, p < 0.05; CI+II: r16 = 0.52, p < 0.05) (Fig. 4a, b).”
Quote in the paperSubstantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
- Findingown data
Play fighting positively correlated with complex I-dependent respiration measured in the amygdala when taking into account all data together.
“Play fighting positively correlated with complex I- and complex II-dependent respiration measured in the amygdala, when taking into account all data together (a, b).”
Quote in the paperSubstantial claim - Findingown data
Play fighting positively correlated with complex II-dependent respiration measured in the amygdala when taking into account all data together.
“Play fighting positively correlated with complex I- and complex II-dependent respiration measured in the amygdala, when taking into account all data together (a, b).”
Quote in the paperSubstantial claim - Findingown data
Among PPS rats, the high player subgroup shows higher play fighting than both control rats and PPS low players.
“Following this approach, we found that whereas play levels in the PPS low player group were similar to CTRLs, in the PPS high player group they were significantly higher than both CTRL and PPS low player animals (all, p < 0.001).”
Quote in the paperSubstantial claim - Findingown data
PPS high and low players do not differ in plasma corticosterone levels following the first stressor exposure on P28.
“whereas plasma corticosterone levels did not differ for the two groups following the first exposure to stress (P28) (Fig. 1j; U = 4.00, n.s.;)”
Quote in the paperNot a substantial claim - Findingown data
PPS high players exhibit higher mitochondrial respiration in each analyzed mitochondrial parameter than control and PPS low player rats in the amygdala.
“Analyses based on the stratification for play fighting levels revealed that PPS high player individuals exhibited higher mitochondrial respiration in each of the mitochondrial parameters analyzed than CTRL and PPS low player rats (all p < 0.01) in the amygdala (Fig. 3f).”
Quote in the paperSubstantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
- Findingown data
Peripubertal stress (PPS) leads to enhanced play fighting at adolescence in rats.
“We report that, indeed, PPS leads to enhanced play fighting at adolescence.”
- Also stated in: § Exposure to PPS leads to enhanced play fighting · plain
“We found that, indeed, PPS rats showed significantly higher play fighting than CTRL animals, both for the compound index (Fig. 1b; U = 252.00, p < 0.01) and, individually, for each of the respective play fighting behaviors”
Quote in the paperSubstantial claim - Also stated in: § Exposure to PPS leads to enhanced play fighting · plain
- Findingown data
PPS low players show higher CB1 gene expression in the nucleus accumbens shell than control rats.
“and PPS low players showed higher CB1 expression than CTRLs (H(3) = 8.50, p < 0.01, post hoc analyses p < 0.05; Fig. 2d).”
Quote in the paperNot a substantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
There are no significant differences between groups in CB1 gene expression in the nucleus accumbens core.
“Similarly, in the NAc core, no significant differences between groups were observed (Fig. 2c; t18 = 1.45, n.s. even when just the two PPS groups were compared: all p > 0.05).”
Quote in the paperNot a substantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
There are no significant differences in the expression levels of MFN2, PGC1α, SIRT1, or TOMM20 in the basolateral amygdala or central amygdala after PPS.
“However, no significant differences were observed for the expression levels of any of the analyzed genes in the BLA (Figure S6) or in the central amygdala (Figure S7).”
Quote in the paperNot a substantial claim - Findingown data
PPS rats exhibit a shorter latency to play fight than control rats at adolescence.
“PPS rats also exhibited shorter latency to play fight than CTRLs (Fig. 1d; U = 270.00, p < 0.05).”
Quote in the paperSubstantial claim - Findingown data
There is no evidence for a link between CB1 expression levels in the BLA, NAc shell, or NAc core and the level of play fighting behaviors in PPS animals.
“We also performed correlational analyses and obtained no evidence to support a link between CB1 expression levels in each of the brain regions in PPS animals and the level of play fighting behaviors (Figure S3).”
Quote in the paperNot a substantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
PPS rats that show low play fighting levels have an increase in CB1 gene expression in the NAc shell.
“we found an increase in CB1 gene expression in the NAc shell of peripubertally stressed rats that show low, but not in those with high play fighting levels.”
Quote in the paperSubstantial claim - Findingown data
The increase in mitochondrial respiration in the amygdala corresponds to PPS high, but not low, fighting rats.
“when assessing mitochondrial respiratory capacity in the amygdala immediately after testing animals for play behavior, we found a marked increase in mitochondria respiration in PPS animals, corresponding to the high, but not low, fighting rats.”
Quote in the paperSubstantial claim - Findingown data
PPS low players show an increased percentage of attacks compared to control rats in the resident-intruder test at adulthood.
“with post-tests revealing an increase in attacks in PPS low players compared to CTRL rats (p < 0.05).”
Quote in the paperSubstantial claim - Findingown data
PPS rats that show high play fighting levels do not have an increase in CB1 gene expression in the NAc shell.
“we found an increase in CB1 gene expression in the NAc shell of peripubertally stressed rats that show low, but not in those with high play fighting levels.”
Quote in the paperSubstantial claim - Findingown data
Both peripubertally stressed groups show increased passive coping responses at adulthood.
“although both peripubertally stressed groups show reduced sociability and increased passive coping responses at adulthood, only those individuals with particularly heightened levels of play fighting are the ones that show abnormal forms of aggression.”
Quote in the paperNot a substantial claim - Findingown data
PPS high players show lower plasma corticosterone levels than PPS low players following stressor exposure on P30 (third stress day).
“the high player group showed markedly lower corticosterone levels than the low player group following stressor exposure to the third day (P30) (Fig. 1j; U = 0.00, p < 0.01).”
Quote in the paperNot a substantial claim - Findingown data
There are no group differences in CB1 gene expression in the basolateral amygdala.
“No group differences in gene expression were found in the BLA (Fig. 2b; t20 = 0.12, n.s., even when just the two PPS groups were compared: all p > 0.05).”
Quote in the paperNot a substantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
Play fighting parameters at adolescence (total play fighting, boxing) positively correlate with specific aggressive behaviors at adulthood (keeping down, abnormal attacks).
“Interestingly, we found positive correlations between play fighting parameters at adolescence (i.e., total play fighting, boxing) and specific types of aggressive behaviors at adulthood (i.e., keeping down, abnormal attacks) (Figure S1a–c).”
Quote in the paperSubstantial claim - Findingown data
Gene expression of TOMM20 in the amygdala homogenates did not correlate with respirometry parameters from amygdala measurement.
“Gene expression of TOMM20 in the amygdala homogenates did not correlate with respirometry parameters from amygdala measurement (c, d), whereas it positively correlated with nucleus accumbens (NAc) data (e, f).”
Quote in the paperNot a substantial claim - Findingown data
Stress exposure at peripuberty leads to enhanced play fighting at adolescence.
“Here, we show that stress exposure at peripuberty leads to enhanced play fighting at adolescence.”
Quote in the paperSubstantial claim - Findingown data
A main effect of stress was found in mitochondrial respiration in the amygdala, with maximal electron transfer system capacity significantly higher in PPS rats than CTRLs.
“A main effect of stress was found in the mitochondrial respiration in the amygdala and the maximal electron transfer system capacity being significantly higher in PPS rats than CTRLs (c).”
Quote in the paperSubstantial claim - Findingown data
CB1 gene expression in the nucleus accumbens shell is higher in PPS rats than in control rats.
“In the NAc shell, CB1 expression levels were higher in PPS animals than in CTRLs (Fig. 2d, t20 = 3.27, p < 0.01)”
Quote in the paperSubstantial claim- Rests on an assumption: CB1 gene expression levels reflect functional CB1 receptor signaling.
- Findingown data
Plasma corticosterone levels on the third day of stress exposure were substantially lower in high than in low play fighting rats.
“High play fighters also show a high degree of adaptation of their corticosterone responses to repeated exposure to stressors during the peripubertal period; i.e., plasma corticosterone levels on the third day of stress exposure were substantially lower in high than in low play fighting rats.”
Quote in the paperNot a substantial claim - Findingown data
No significant change was observed in respiration in the NAc in the analysis according to play fighting level.
“Moreover, amygdala respiration was increased in PPS high players compared to CTRLs and PPS low players (f), whereas no significant change was observed in the respiration in the NAc (g).”
Quote in the paperNot a substantial claim - Findingown data
PPS high players showed higher play fighting than CTRLs.
“Analysis according to play fighting level confirmed that PPS high players showed higher play fighting than to CTRLs (e).”
Quote in the paperSubstantial claim - Findingown data
PPS and control rats do not differ in social exploration during the play fighting encounter at adolescence.
“However, the two groups did not differ in social exploration during the encounter (Fig. 1e; t56 = 1.19, n.s.).”
Quote in the paperNot a substantial claim - Findingown data
PPS animals show a marked increase in mitochondrial respiration in the amygdala immediately after testing for play behavior.
“when assessing mitochondrial respiratory capacity in the amygdala immediately after testing animals for play behavior, we found a marked increase in mitochondria respiration in PPS animals, corresponding to the high, but not low, fighting rats.”
Quote in the paperSubstantial claim - Findingown data
Gene expression of TOMM20 in the amygdala homogenates positively correlated with nucleus accumbens (NAc) data.
“Gene expression of TOMM20 in the amygdala homogenates did not correlate with respirometry parameters from amygdala measurement (c, d), whereas it positively correlated with nucleus accumbens (NAc) data (e, f).”
Quote in the paperNot a substantial claim - Findingown data
Amygdala respiration was increased in PPS high players compared to CTRLs and PPS low players.
“Moreover, amygdala respiration was increased in PPS high players compared to CTRLs and PPS low players (f), whereas no significant change was observed in the respiration in the NAc (g).”
Quote in the paperSubstantial claim - Findingown data
PPS rats with high and low levels of play fighting show similar increases in passive depression-like behaviors (increased floating in the forced swim test) at adulthood.
“Here, we confirm and extend these findings by showing that rats with high and low levels of play fighting at adolescence show similar alterations in sociability (i.e., reduced social exploration) and passive depression-like behaviors (increased floating in the forced swim test) and defensive aggression (increased attack numbers in the resident-intruder test) at adulthood.”
Quote in the paperSubstantial claim - Findingown data
Amygdala mitochondrial respiration and play fighting percentage correlated positively.
“Strikingly, amygdala mitochondrial respiration and play fighting percentage correlated positively.”
Quote in the paperSubstantial claim - Findingown data
PPS rats with high and low levels of play fighting show similar increases in defensive aggression (increased attack numbers in the resident-intruder test) at adulthood.
“Here, we confirm and extend these findings by showing that rats with high and low levels of play fighting at adolescence show similar alterations in sociability (i.e., reduced social exploration) and passive depression-like behaviors (increased floating in the forced swim test) and defensive aggression (increased attack numbers in the resident-intruder test) at adulthood.”
Quote in the paperSubstantial claim - Findingown data
PPS rats with high and low levels of play fighting at adolescence show similar reductions in social exploration at adulthood.
“Here, we confirm and extend these findings by showing that rats with high and low levels of play fighting at adolescence show similar alterations in sociability (i.e., reduced social exploration) and passive depression-like behaviors (increased floating in the forced swim test) and defensive aggression (increased attack numbers in the resident-intruder test) at adulthood.”
Quote in the paperSubstantial claim - Findingown data
Animals with higher levels of play fighting showed better adaptation to PPS.
“Corticosterone analyses revealed that animals with higher levels of play fighting showed better adaptation to PPS.”
Quote in the paperSubstantial claim - Findingown data
Stressed high players at adolescence specifically show increased forms of abnormal behaviors.
“Importantly, we identify stressed high players at adolescence as the ones that specifically show increased forms of abnormal behaviors.”
Quote in the paperSubstantial claim - Findingown data
Levels of play fighting do not predict total levels of adult aggressive behavior.
“Our findings support the view that whereas the levels of play fighting do not predict total levels of adult aggressive behavior, high levels of play behavior induced by stress are associated with abnormal forms of adult aggression.”
Quote in the paperSubstantial claim - Findingnone given
These animals show a drastic increase in mitochondrial respiration in the amygdala following play fighting.
“In addition, these animals show a drastic increase in mitochondrial respiration in the amygdala following play fighting.”
Quote in the paperSubstantial claim - Interpretationown data
PPS individuals with heightened play fighting at adolescence are the ones that show abnormal forms of aggression at adulthood.
“Using a stratification approach, we identify individuals with heightened levels of play fighting as the ones that show abnormal forms of aggression at adulthood.”
Quote in the paperSubstantial claim - Interpretationown data
Brain energy metabolism during adolescence is a possible target to prevent adult aggression.
“They also point at brain energy metabolism during adolescence as a possible target to prevent adult aggression.”
Quote in the paperNot a substantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
- Interpretationown data
Adolescence is a potential critical period in which aberrant play fighting is linked to the emergence of adult aggression.
“Our results highlight adolescence as a potential critical period in which aberrant play fighting is linked to the emergence of adult aggression.”
Quote in the paperSubstantial claim - Interpretationown data
High play fighting PPS rats show a high degree of adaptation of their corticosterone responses to repeated exposure to stressors during the peripubertal period.
“High play fighters also show a high degree of adaptation of their corticosterone responses to repeated exposure to stressors during the peripubertal period; i.e., plasma corticosterone levels on the third day of stress exposure were substantially lower in high than in low play fighting rats.”
Quote in the paperSubstantial claim - Interpretationown data
High levels of play behavior induced by stress are associated with abnormal forms of adult aggression.
“Our findings support the view that whereas the levels of play fighting do not predict total levels of adult aggressive behavior, high levels of play behavior induced by stress are associated with abnormal forms of adult aggression.”
Quote in the paperSubstantial claim
- Probably not a substantial claim. 30
- It may state two separate claims as one. 23
- The quote only partly states this claim. 1
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationPrevious work from the authors' lab demonstrated that peripubertally stressed adult rats show deficits in social behaviors, including reduced sociability and heightened aggression.
“Previous work has demonstrated deficits in social behaviors, including reduced sociability and heightened aggression, in peripubertally stressed adult rats13–16.”
Quote in the paperNot a substantial claim4 of 4 sources checked- cites [13] Cordero, M. I. et al. Evidence for biological roots in the transgenerational transmission of intimate partner violence. Transl. Psychiatry 2, e106 (2012). source
The Results section (‘Effects of peripuberty stress on males’ aggressive behavior against females at adulthood’; page unavailable) reports that peripubertally stressed males were more aggressive toward females than controls. The passages found do not report reduced sociability in those males, so the citation supports the aggression component but not both stated social-behavior deficits. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [14] Márquez, C. et al. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression. Transl. Psychiatry 3, e216 (2013). source
- cites [15] Tzanoulinou, S. et al. Long-term behavioral programming induced by peripuberty stress in rats is accompanied by GABAergic-related alterations in the Amygdala. PLoS ONE 9, e94666 (2014). source
- cites [16] Tzanoulinou, S., Riccio, O., de Boer, M. W. & Sandi, C. Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala. Transl. Psychiatry 4, e410 (2014). source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationEarly life stress elicits both increased play fighting and adult aggressive behaviors in different species.
“This finding is consistent with former observations in different species showing that both increased play fighting and adult aggressive behaviors are elicited by early life stress.”
Quote in the paperNot a substantial claim1 of 5 sources checked- cites [8] Veenema, A. H. & Neumann, I. D. Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats. Psychoneuroendocrinology 34, 463–467 (2009). source
- cites [29] Veenema, A. H., Blume, A., Niederle, D., Buwalda, B. & Neumann, I. D. Effects of early life stress on adult male aggression and hypothalamic vasopressin and serotonin. Eur. J. Neurosci. 24, 1711–1720 (2006). source
- cites [12] Wommack, J. C., Taravosh-Lahn, K., David, J. T. & Delville, Y. Repeated exposure to social stress alters the development of agonistic behavior in male golden hamsters. Horm. Behav. 43, 229–236 (2003). source
- cites [37] Wommack, J. C. & Delville, Y. Repeated social stress and the development of agonistic behavior: individual differences in coping responses in male golden hamsters. Physiol. Behav. 80, 303–308 (2003). source
- cites [38] Weder, N. et al. MAOA genotype, maltreatment, and aggressive behavior: the changing impact of genotype at varying levels of trauma. Biol. Psychiatry 65, 417–424 (2009). source
The Results (TTES; page unavailable) link childhood trauma with aggression scores in children, supporting an association between early adversity and aggression. The paper does not establish increased play fighting, adult aggression, or observations across different species; its findings also do not establish that stress elicits those behaviors. (LLM, conf=0.88)
Experimental — accuracy not yet measured
It may state two separate claims as one.
PremisecitationThe endocannabinoid system is implicated in the regulation of the HPA axis and play behavior.
“The endocannabinoid system has been implicated in a myriad of functions, including the regulation of the HPA axis21,22 and play behavior.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [21] Hill, M. N. & McEwen, B. S. Involvement of the endocannabinoid system in the neurobehavioural effects of stress and glucocorticoids. Prog. Neuropsychopharmacol. Biol. Psychiatry 34, 791–797 (2010). source
- cites [22] Tasker, J. G. & Herman, J. P. Mechanisms of rapid glucocorticoid feedback inhibition of the hypothalamic–pituitary–adrenal axis. Stress Amst. Neth. 14, 398–406 (2011). source
It may state two separate claims as one.
PremisecitationCorticosterone administration at the same schedule as the PPS model mimics alterations in the social domain and leads to enhanced play fighting.
“Interestingly, corticosterone administration at the exact schedule as our peripubertal stress (PPS) model mimicked alterations in the social domain and led as well to enhanced play fighting17.”
Quote in the paperSubstantial claim1 of 1 sources checked- cites [17] Veenit, V., Cordero, M. I., Tzanoulinou, S. & Sandi, C. Increased corticosterone in peripubertal rats leads to long-lasting alterations in social exploration and aggression. Front. Behav. Neurosci. 7, 26 (2013). source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationSystemic injection of an endocannabinoid agonist increases play fighting through actions on the CB1 receptor, and the nucleus accumbens and basolateral amygdala are implicated in these effects.
“Systemic injection of an endocannabinoid agonist was shown to increase play fighting though actions on the CB1 receptor, and the nucleus accumbens (NAc) and basolateral amygdala (BLA) have been implicated in these effects23,24.”
Quote in the paperSubstantial claim2 of 2 sources checked- cites [23] Manduca, A. et al. Interacting cannabinoid and opioid receptors in the nucleus accumbens core control adolescent social play. Front. Behav. Neurosci. 10, 211 (2016). source
The Results report that systemic JZL184 increased pinning and pouncing in adolescent rats, and that a CB1 receptor antagonist blocked the effect. The Introduction implicates both the nucleus accumbens and basolateral amygdala in endocannabinoid-related social play. But JZL184 is a 2-AG hydrolysis inhibitor, not an injected endocannabinoid agonist. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [24] Trezza, V. et al. Endocannabinoids in amygdala and nucleus accumbens mediate social play reward in adolescent rats.J. Neurosci. Off. J. Soc. Neurosci. 32, 14899–14908 (2012). source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationEarly-life stress has been shown to alter play fighting in rats and hamsters and to increase aggressive behaviors at adulthood.
“Early-life stress has been shown to alter play fighting in rats and hamsters as well as to increase aggressive behaviors at adulthood.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [8] Veenema, A. H. & Neumann, I. D. Maternal separation enhances offensive play-fighting, basal corticosterone and hypothalamic vasopressin mRNA expression in juvenile male rats. Psychoneuroendocrinology 34, 463–467 (2009). source
- cites [10] Varlinskaya, E. I., Truxell, E. M. & Spear, L. P. Repeated restraint stress alters sensitivity to the social consequences of ethanol differentially in early and late adolescent rats. Pharmacol. Biochem. Behav. 113, 38–45 (2013). source
The Results (§3.2; page not provided) report that juvenile restraint stress increased play fighting in early-adolescent male rats. The paper provides no finding about hamsters or increased aggression in adulthood; Methods (§2.6; page not provided) says serious fighting was not analyzed. (LLM, conf=0.90)
Experimental — accuracy not yet measured - cites [12] Wommack, J. C., Taravosh-Lahn, K., David, J. T. & Delville, Y. Repeated exposure to social stress alters the development of agonistic behavior in male golden hamsters. Horm. Behav. 43, 229–236 (2003). source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationCB1 receptors are expressed in the mitochondrial membrane, where they act on the regulation of energy metabolism and mitochondrial functions.
“Importantly, CB1 receptors have been shown to be expressed in the mitochondrial membrane, where they act on the regulation of energy metabolism and mitochondrial functions25–27.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [25] Bénard, G. et al. Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nat. Neurosci. 15, 558–564 (2012). source
- cites [26] Hebert-Chatelain, E. et al. Cannabinoid control of brain bioenergetics: exploring the subcellular localization of the CB1 receptor. Mol. Metab. 3, 495–504 (2014). source
- cites [27] Hebert-Chatelain, E. et al. A cannabinoid link between mitochondria and memory. Nature 539, 555–559 (2016). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationIntra-NAc infusion of the mu-opioid receptor agonist DAMGO or amphetamine leads to enhanced play fighting when injected either into the core or into the shell.
“Furthermore, intra-NAc infusion of the mu-opioid receptor agonist DAMGO or amphetamine leads to enhanced play fighting when injected either into the core or into the shell19,56.”
Quote in the paperNot a substantial claim2 of 2 sources checked- cites [19] Trezza, V., Damsteegt, R., Achterberg, E. J. M. & Vanderschuren, L. J. M. J. Nucleus accumbens μ-opioid receptors mediate social reward. J. Neurosci. 31, 6362–6370 (2011). source
- cites [56] Manduca, A. et al. Dopaminergic neurotransmission in the nucleus accumbens modulates social play behavior in rats. Neuropsychopharmacology 41, 2215–2223 (2016). source
The Discussion (page not available in our copy) says pilot infusions of amphetamine into both the NAc core and shell stimulated social play. It also discusses local opioid signaling in those subregions, but does not identify DAMGO or report that DAMGO infusion enhanced play fighting in both. (LLM, conf=0.87)
Experimental — accuracy not yet measured
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationA particularly severe subgroup of children with antisocial behavior show hypoactivity of the hypothalamus-pituitary-adrenal axis.
“However, our findings align well with evidence that a particularly severe subgroup of children with antisocial behavior show hypoactivity of the hypothalamus-pituitary-adrenal axis50,51.”
Quote in the paperNot a substantial claim1 of 2 sources checked- cites [50] Northover, C., Thapar, A., Langley, K., Fairchild, G. & van Goozen, S. H. M. Cortisol levels at baseline and under stress in adolescent males with attention-deficit hyperactivity disorder, with or without comorbid conduct disorder. Psychiatry Res. 242, 130–136 (2016). source
The Discussion (page not provided) reports that low HPA-axis activity under stress was more apparent in adolescent boys with ADHD who had more severe conduct problems. The claim omits that population and stress-specific qualification: the paper explicitly says conduct disorder was not associated with HPA-axis hypoactivity at baseline. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [51] Hawes, D. J., Brennan, J. & Dadds, M. R. Cortisol, callous-unemotional traits, and pathways to antisocial behavior. Curr. Opin. Psychiatry 22, 357–362 (2009). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationIn children, cortisol moderates the association between early life stress and persistent childhood aggression, with the ELS-aggression relationship being stronger among children who had higher levels of cortisol reactivity during the preschool period.
“However, this data is at odds with recent data from children indicating a moderating role of cortisol in the association between early life stress and persistent childhood aggression, with the ELS-aggression relationship being stronger among children who had higher levels of cortisol reactivity during the preschool period49.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [49] Winiarski, D. A., Engel, M. L., Karnik, N. S. & Brennan, P. A. Early life stress and childhood aggression: mediating and moderating effects of child callousness and stress reactivity. Child Psychiatry Hum. Dev. 49, 1–10 (2018). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationPrevious work showed that differences in mitochondrial function in the amygdala do not seem to be relevant for fast fear conditioning associations.
“Although very little is known regarding the implication of differences in mitochondrial function in the amygdala for social behaviors, previous work showed that it does not seem to be relevant for fast fear conditioning associations32.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [32] Hollis, F. et al. Mitochondrial function in the brain links anxiety with social subordination. Proc. Natl. Acad. Sci. USA. 112, 15486–15491 (2015). source
It may state two separate claims as one.
PremisecitationPPS in rats leads to reduced sociability, increased depression-like behaviors, and increased forms of abnormal aggression.
“Previously, we had reported reduced sociability, increased depression-like behaviors and increased forms of abnormal aggression following PPS in rats13–16,34,35,36.”
Quote in the paperSubstantial claim4 of 7 sources checked- cites [13] Cordero, M. I. et al. Evidence for biological roots in the transgenerational transmission of intimate partner violence. Transl. Psychiatry 2, e106 (2012). source
The Results section on males’ aggressive behavior reports that peripubertally stressed males were more aggressive toward females than controls. The Results section on female partners reports increased depression-like behavior after cohabitation, but that finding concerns the females, not the stressed males. The passages do not establish reduced sociability in the stressed males. (LLM, conf=0.87)
Experimental — accuracy not yet measured - cites [14] Márquez, C. et al. Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression. Transl. Psychiatry 3, e216 (2013). source
- cites [15] Tzanoulinou, S. et al. Long-term behavioral programming induced by peripuberty stress in rats is accompanied by GABAergic-related alterations in the Amygdala. PLoS ONE 9, e94666 (2014). source
The Results section reports reduced social exploration in PPS rats, and the Discussion says PPS animals were also found to display pathological aggression. Our copy reports increased anxiety-like behavior, but does not report increased depression-like behavior; that part of the attributed claim is unsupported. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [16] Tzanoulinou, S., Riccio, O., de Boer, M. W. & Sandi, C. Peripubertal stress-induced behavioral changes are associated with altered expression of genes involved in excitation and inhibition in the amygdala. Transl. Psychiatry 4, e410 (2014). source
The Introduction describes decreased sociability and pathological aggression after peripubertal stress in rats, and the Results report reduced social preference and increased total aggression after the full protocol. The paper describes increased anxiety, not increased depression-like behavior, so that part of the attributed claim is unsupported. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measured - cites [34] Cordero, M. I., Just, N., Poirier, G. L. & Sandi, C. Effects of paternal and peripubertal stress on aggression, anxiety, and metabolic alterations in the lateral septum. Eur. Neuropsychopharmacol. 26, 357–367 (2016). source
- cites [35] Veenit, V., Riccio, O. & Sandi, C. CRHR1 links peripuberty stress with deficits in social and stress-coping behaviors. J. Psychiatr. Res. 53, 1–7 (2014). source
- cites [36] Walker, S. E. & Sandi, C. Long-term programing of psychopathology-like behaviors in male rats by peripubertal stress depends on individual’s glucocorticoid responsiveness to stress. Stress 0, 1–10 (2018). source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationOnly pharmacological inactivation of the NAc core, but not shell, interfered with social play behavior.
“A pronounced increase in c-Fos expression has been observed in both the NAc core and shell following play fighting in rats54; however, only pharmacological inactivation of the NAc core, but not shell, interfered with social play behavior55.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [55] van Kerkhof, L. W., Damsteegt, R., Trezza, V., Voorn, P. & Vanderschuren, L. J. Social play behavior in adolescent rats is mediated by functional activity in medial prefrontal cortex and striatum. Neuropsychopharmacology 38, 1899–1909 (2013). source
In “Pharmacological Inactivation of Striatal Regions,” NAcc core inactivation increased total play time, while a lower, non-disruptive dose in the shell had no measured effect. The categorical “but not shell” overstates the comparison: the dose used in the core completely blocked play when given in the shell, although the authors attribute that blockade to intense eating rather than a direct effect on social play. (LLM, conf=0.83)
Experimental — accuracy not yet measured
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationCB1 receptors are expressed in mitochondria where they regulate energy metabolism and mitochondrial functions.
“Recently, CB1 receptors were shown to be expressed in mitochondria where they regulate energy metabolism and mitochondrial functions25–27.”
Quote in the paperSubstantial claim1 of 3 sources checked- cites [25] Bénard, G. et al. Mitochondrial CB1 receptors regulate neuronal energy metabolism. Nat. Neurosci. 15, 558–564 (2012). source
- cites [26] Hebert-Chatelain, E. et al. Cannabinoid control of brain bioenergetics: exploring the subcellular localization of the CB1 receptor. Mol. Metab. 3, 495–504 (2014). source
- cites [27] Hebert-Chatelain, E. et al. A cannabinoid link between mitochondria and memory. Nature 539, 555–559 (2016). source
Probably not a substantial claim. It may state two separate claims as one.
PremisecitationMitochondria function and energy metabolism in the NAc is implicated in social competition and vulnerability to social defeat.
“Mitochondria function and energy metabolism in the NAc was also recently implicated in social competition32,33 and vulnerability to social defeat57.”
Quote in the paperSubstantial claim2 of 3 sources checked- cites [32] Hollis, F. et al. Mitochondrial function in the brain links anxiety with social subordination. Proc. Natl. Acad. Sci. USA. 112, 15486–15491 (2015). source
- cites [33] van der Kooij, M. A. et al. Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors. Mol. Psychiatry 23, 569–578 (2018). source
- cites [57] Larrieu, T. et al. Hierarchical status predicts behavioral vulnerability and nucleus accumbens metabolic profile following chronic social defeat stress. Curr. Biol. 27, 2202–2210.e4 (2017). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationA pronounced increase in c-Fos expression has been observed in both the NAc core and shell following play fighting in rats.
“A pronounced increase in c-Fos expression has been observed in both the NAc core and shell following play fighting in rats54; however, only pharmacological inactivation of the NAc core, but not shell, interfered with social play behavior55.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [54] van Kerkhof, L. W. M. et al. Cellular activation in limbic brain systems during social play behaviour in rats. Brain. Struct. Funct. 219, 1181–1211 (2014). source
Probably not a substantial claim. It may be too vague to check against evidence. The paper’s conclusions may not depend on it.
PremisecitationThe stratification approach followed is in line with an emerging trend in the literature, taking into account individual differences in behavioral outcomes when examining underlying neurobiology.
“We should briefly note that the stratification approach that we have followed is in line with an emerging trend in the literature, taking into account individual differences in behavioral outcomes when examining underlying neurobiology36,39–44.”
Quote in the paperNot a substantial claim4 of 7 sources checked- cites [36] Walker, S. E. & Sandi, C. Long-term programing of psychopathology-like behaviors in male rats by peripubertal stress depends on individual’s glucocorticoid responsiveness to stress. Stress 0, 1–10 (2018). source
- cites [39] Anacker, C. et al. Neuroanatomic differences associated with stress susceptibility and resilience. Biol. Psychiatry 79, 840–849 (2016). source
- cites [40] Krishnan, V. et al. Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions. Cell 131, 391–404 (2007). source
- cites [41] Nasca, C., Bigio, B., Zelli, D., Nicoletti, F. & McEwen, B. S. Mind the gap: glucocorticoids modulate hippocampal glutamate tone underlying individual differences in stress susceptibility. Mol. Psychiatry 20, 755–763 (2015). source
- cites [42] Nasca, C. et al. Role of the astroglial glutamate exchanger xCT in ventral hippocampus in resilience to stress. Neuron 96, 402–413.e5 (2017). source
- cites [43] Ritov, G., Boltyansky, B. & Richter-Levin, G. A novel approach to PTSD modeling in rats reveals alternating patterns of limbic activity in different types of stress reaction. Mol. Psychiatry 21, 630–641 (2016). source
- cites [44] Takahashi, A. et al. Establishment of a repeated social defeat stress model in female mice. Sci. Rep. 7, 12838 (2017). source
- Rests on an assumption: Most studies so far have dealt with group effects, not considering individual differences in developmental trajectories from play fighting to adult aggression.
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationStudies of children exposed to maltreatment have reported alterations in amygdala reactivity, including increased amygdala reactivity in response to angry faces and during pre-attentive emotional processing, while hypoactivation to social rejection cues.
“In this connection, it is relevant to note that studies of children exposed to maltreatment have reported alterations in amygdala reactivity, including increased amygdala reactivity in response to angry faces62 and during pre-attentive emotional processing63 while hypoactivation to social rejection cues64.”
Quote in the paperNot a substantial claim2 of 3 sources checked- cites [62] McCrory, E. J. et al. Heightened neural reactivity to threat in child victims of family violence. Curr. Biol. 21, R947–R948 (2011). source
- cites [63] McCrory, E. J. et al. Amygdala activation in maltreated children during pre-attentive emotional processing. Br. J. Psychiatry 202, 269–276 (2013). source
- cites [64] Puetz, V. B. et al. Altered neural response to rejection-related words in children exposed to maltreatment. J. Child Psychol. Psychiatry 57, 1165–1173 (2016). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationWithin-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats.
“Interestingly, a previous study showed that within-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats70.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [70] van Hasselt, F. N. et al. Within-litter variation in maternal care received by individual pups correlates with adolescent social play behavior in male rats. Physiol. Behav. 106, 701–706 (2012). source
Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationModerate recurrent hypoglycemia during the pre-weaning period led to abnormal responses to stress and decreases in adolescent social play behavior.
“Another study showed that the moderate recurrent hypoglycemia during the pre-weaning period led to abnormal responses to stress and decreases in adolescent social play behavior60.”
Quote in the paperNot a substantial claim1 of 1 sources checked- cites [60] Moore, H. et al. Moderate recurrent hypoglycemia during early development leads to persistent changes in affective behavior in the rat. Brain Behav. Immun. 24, 839–849 (2010). source
It may state two separate claims as one. The quote only partly states this claim.
Findingown dataPPS high players exhibit increased duration of pinning, pouncing, boxing, and kicking and a shorter latency to play fight compared to controls and PPS low players.
“The same picture was observed when each play fighting parameter was evaluated independently (pinning: F(2, 57) = 9.80, p < 0.001; pouncing: H(3) = 18.49, p < 0.001; boxing; H(3) = 12.67, p < 0.01; kicking; H(3) = 16.59, p < 0.001, post hoc analyses p < 0.01 or p < 0.001; Fig. 1g).”
- Also stated in: § Exposure to PPS leads to enhanced play fighting · plain
“The latency to play fight was also different between the three groups (Fig. 1h; H(3) = 6.52, p < 0.05) due to a shorter latency in PPS high player rats than CTRLs (p < 0.05).”
Quote in the paperSubstantial claim- Also stated in: § Exposure to PPS leads to enhanced play fighting · plain
It may state two separate claims as one.
Findingown dataPPS increases play fighting in rats, leading to enhanced duration of a diversity of play behaviors including pinning, pouncing boxing, and kicking.
“Our data shows that PPS increases play fighting in rats, leading to enhanced duration of a diversity of play behaviors including pinning, pouncing boxing, and kicking.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataPPS leads to enhanced mitochondrial respiration in the amygdala, but not in the nucleus accumbens, when measured ex vivo after the play fighting test.
“Strikingly, a main effect of stress was found in ex vivo measurements of mitochondrial respiration in the amygdala (Fig. 3c; F(1, 56) = 7.56, p < 0.01) but not in the NAc (Fig. 3d; F(1, 56) = 2.86, n.s.).”
Quote in the paperSubstantial claim- Rests on an assumption: Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
It may state two separate claims as one.
Findingown dataStressed animals showed enhanced respiration in the amygdala but not in the NAc.
“Stressed animals showed enhanced respiration in the amygdala but not in the NAc.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataPPS led to an increase in CB1 mRNA levels in the NAc shell-but not in NAc core or in the BLA-that was particularly apparent in PPS low players.
“PPS led to an increase in CB1 mRNA levels in the NAc shell—but not in NAc core or in the BLA—that was particularly apparent in PPS low players.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Findingown dataPPS increases play fighting, particularly in a subgroup of rats that rapidly show blunted corticosterone responses to repeated stressor exposure and display abnormal behaviors at adulthood.
“In conclusion, we report here that PPS increases play fighting, particularly in a subgroup of rats that rapidly show blunted corticosterone responses to repeated stressor exposure and display abnormal behaviors at adulthood.”
Quote in the paperSubstantial claimProbably not a substantial claim.
Study design and conductnone givenMale rats from different litters were randomly assigned to control and PPS conditions at weaning.
“At weaning, male rats from different litters were randomly assigned to control (CTRL) and PPS conditions.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductnone givenThe sample size was calculated following previous studies from the authors' lab with the PPS model and estimated to be between 8 and 12.
“The sample size was calculated following previous studies from our lab with the PPS model and estimated to be between 8 and 12.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
Study design and conductreasoningThe experimenter was blind during testing and analysis, including manual scoring of play fighting behaviors.
“The experimenter was blind during both testing and analysis.”
- Also stated in: § Play fighting test · plain
“The interaction was video-recorded and behaviors were manually scored offline by a trained experimenter blind to experimental groups, which was assisted by the Observer software (Noldus IT; Netherlands).”
Quote in the paperNot a substantial claim- Also stated in: § Play fighting test · plain
It may state two separate claims as one.
Study design and conductown dataThe increase in CB1 expression observed in the NAc of PPS rats relates to the total pool of CB1 transcripts; no conclusion can be established regarding the effect of PPS on mitochondrial CB1 expression.
“We should note, however, that the increase in CB1 expression that we observed in the NAc of PPS rats relates to the total pool of CB1 transcripts; accordingly, no conclusion can be established regarding the effect of PPS in mitochondrial CB1 expression.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationConstitutively high-but not low-habituating rats exposed to PPS were the only ones that developed abnormal signs of aggression.
“Specifically, we recently reported that constitutively high—but not low—habituating rats exposed to PPS were the only ones that developed abnormal signs of aggression45.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [45] Walker, S. E., Zanoletti, O., Guillot de Suduiraut, I. & Sandi, C. Constitutive differences in glucocorticoid responsiveness to stress are related to variation in aggression and anxiety-related behaviors. Psychoneuroendocrinology 84, 1–10 (2017). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationChronic glucocorticoid deficiency induces abnormal aggression in rats.
“In addition, these findings resonate with earlier work by Haller and collaborators in rats showing that chronic glucocorticoid deficiency induces abnormal aggression46–48.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [46] Haller, J., Halász, J., Mikics, É. & Kruk, M. R. Chronic glucocorticoid deficiency-induced abnormal aggression, autonomic hypoarousal, and social deficit in rats. J. Neuroendocrinol. 16, 550–557 (2004). source
- cites [47] Haller, J., van de Schraaf, J. & Kruk, M. R. Deviant forms of aggression in glucocorticoid hyporeactive rats: a model for “pathological” aggression? J. Neuroendocrinol. 13, 102–107 (2001). source
- cites [48] Tulogdi, A. et al. Brain mechanisms involved in predatory aggression are activated in a laboratory model of violent intra-specific aggression. Eur. J. Neurosci. 32, 1744–1753 (2010). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
Study design and conductreasoningGiven that we cannot identify the cell type in which changes in CB1 mRNA expression take place, changes in mitochondrial function related to potential interactions with CB1 might not necessarily be detected within the NAc.
“Given that we cannot identify the cell type in which changes in CB1 mRNA expression take place, changes in mitochondrial function related to potential interactions with CB1 might not necessarily be detected within the NAc.”
Quote in the paperNot a substantial claimProbably not a substantial claim.
Study design and conductnone givenFunctional mitochondrial measurements reflect maximal O2 consumption ex vivo when mitochondria are provided with excess substrates for each tested complex.
“Although it is tempting to speculate that the observed differences arise from behavioral differences displayed during the play behavior test given right before brain samples were taken, it should be noted that the functional mitochondrial measurements reflect maximal O2 consumption ex vivo when mitochondria are provided with excess substrates for each tested complex.”
Quote in the paperSubstantial claimIt may state two separate claims as one.
Study design and conductreasoningThe measurements taken do not necessarily reflect the actual mitochondrial function in vivo before samples were taken, but mitochondrial capacity to functionally respond when electron transport complexes I and II are stimulated with substrates in excess.
“Therefore, the measurements we took do not necessarily reflect the actual mitochondrial function in vivo before samples were taken, but mitochondrial capacity to functionally respond when electron transport complexes I and II are stimulated with substrates in excess.”
Quote in the paperSubstantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
PremisecitationExposure to different metabolic challenges (high-fat diet, caloric restriction, exercise) during the juvenile period led to drastic changes in play behavior and expression of genes involved in bioenergetics in the prefrontal cortex.
“In this vein, it is relevant to note that exposure to different metabolic challenges (i.e., high-fat diet, caloric restriction, exercise) during the juvenile period led to drastic changes in play behavior and expression of genes involved in bioenergetics in the brain region (prefrontal cortex) examined59.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [59] Hehar, H., Ma, I. & Mychasiuk, R. Effects of metabolic programming on juvenile play behavior and gene expression in the prefrontal cortex of rats. Dev. Neurosci. 38, 96–104 (2016). source
Probably not a substantial claim.
PremisecitationSocial play fighting impinges a high metabolic cost to the organism.
“Given that social play fighting impinges a high metabolic cost to the organism58, metabolic differences arising from either early life or through the interaction with stress at puberty might be relevant in this context.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [58] Siviy, S. M. & Atrens, D. M. The energetic costs of rough-and-tumble play in the juvenile rat. Dev. Psychobiol. 25, 137–148 (1992). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationHypo-reactivity of the right amygdala to fearful faces and to theory of mind judgments was reported for children with conduct problems and elevated levels of callous-unemotional traits.
“On the contrary, hypo-reactivity of the right amygdala to fearful faces66 and to theory of mind judgments67 was reported for children with conduct problems and elevated levels of callous-unemotional traits.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [66] Jones, A. P., Laurens, K. R., Herba, C. M., Barker, G. J. & Viding, E. Amygdala hypoactivity to fearful faces in boys with conduct problems and callous-unemotional traits. Am. J. Psychiatry 166, 95–102 (2009). source
- cites [67] Sebastian, C. L. et al. Neural responses to affective and cognitive theory of mind in children with conduct problems and varying levels of callous-unemotional traits. Arch. Gen. Psychiatry 69, 814–822 (2012). source
Probably not a substantial claim. It may be too vague to check against evidence.
InterpretationreasoningThese results highlight adolescence as a potential critical period to prevent adult aggression by targeting heightened levels of play fighting.
“These results highlight adolescence as a potential critical period to prevent adult aggression by targeting heightened levels of play fighting.”
Quote in the paperNot a substantial claimProbably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationThese children frequently display increased aggressive behaviors.
“These children frequently display increased aggressive behaviors65.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [65] Holmes, M. R. Aggressive behavior of children exposed to intimate partner violence: an examination of maternal mental health, maternal warmth and child maltreatment. Child Abus. Negl. 37, 520–530 (2013). source
Probably not a substantial claim. The paper’s conclusions may not depend on it.
PremisecitationEarly postnatal overnutrition was associated with decreases in social play behavior in adolescent male rats.
“Conversely, early postnatal overnutrition was associated with decreases in social play behavior in adolescent male rats61.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [61] Carvalho, A. L. O., Ferri, B. G., de Sousa, F. A. L., Vilela, F. C. & Giusti-Paiva, A. Early life overnutrition induced by litter size manipulation decreases social play behavior in adolescent male rats. Int. J. Dev. Neurosci. 53, 75–82 (2016). source
The paper relies on this without support.
Ex vivo mitochondrial respiration measurements reflect in vivo mitochondrial function in the amygdala.
“Strikingly, a main effect of stress was found in ex vivo measurements of mitochondrial respiration in the amygdala (Fig. 3c; F(1, 56) = 7.56, p < 0.01) but not in the NAc (Fig. 3d; F(1, 56) = 2.86, n.s.).”
The paper relies on this without support.
CB1 gene expression levels reflect functional CB1 receptor signaling.
“In the NAc shell, CB1 expression levels were higher in PPS animals than in CTRLs (Fig. 2d, t20 = 3.27, p < 0.01)”
The paper relies on this without support.
Most studies so far have dealt with group effects, not considering individual differences in developmental trajectories from play fighting to adult aggression.
“However, most studies so far have dealt with group effects, not considering individual differences in developmental trajectories from play fighting to adult aggression.”
The paper relies on this without support.
CB1 is an axonal protein.
“In addition, given that CB1 is an axonal protein, if the expression of CB1 mRNA is changing in projection neurons, as opposed to local interneurons, then changes in CB1 receptor expression would not be locally within the accumbens shell.”
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- ConsistentF(2, 57) = 9.8reported p < .001 · recomputed p < .001
“F(2, 57) = 9.80, p < .001”
- ConsistentF(2, 57) = 2.16reported n.s. · recomputed p = .125
“F(2, 57) = 2.16, n.s.”
- ConsistentF(1, 56) = 7.56reported p < .01 · recomputed p = .008
“F(1, 56) = 7.56, p < .01”
- ConsistentF(1, 56) = 2.86reported n.s. · recomputed p = .096
“F(1, 56) = 2.86, n.s.”
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.
ANOVA degrees of freedom imply more rats than reported
MinorThe figure reports 29 CTRL, 13 PPS low-player, and 17 PPS high-player rats, totaling 59. A three-group ANOVA with 59 observations has 56 residual degrees of freedom, not the reported 57.
“pinning: F(2, 57) = 9.80, p < 0.001”
“except for play fighting data, where CTRL = 29; PPS = 30; PPS low player = 13, and PPS high player = 17.”
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Neurobiological links between stress and anxiety
Daviu, N., Bruchas, M. R., Moghaddam, B., Sandi, C., & Beyeler, A. (2019) · Neurobiology of Stress · doi:10.1016/j.ynstr.2019.100191 · Cited by 528
“Specifically, peri-puberal stress increases play-fighting and increases the chances to display abnormal aggressive behaviors later in adulthood (Papilloud et al., 2018).”
Self-citationAnxiety and Brain Mitochondria: A Bidirectional Crosstalk
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Self-citationThe neurobiology of social play behaviour: Past, present and future
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“In male rats, peripubertal stress was shown to elicit abnormal aggressive behaviors and increased anxiety (Papilloud et al., 2018; Márquez et al., 2013; Walker et al., 2018), as well as alterations in the expression of molecules involved in inhibitory neurotransmission in the medial prefrontal cortex (mPFC) (Tzanoulin…”
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Programming effects of peripubertal stress on spatial learning
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Self-citationAggression, Aggression-Related Psychopathologies and Their Models
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“…increased the level of aggression in adulthood, elicited attacks on vulnerable body parts of opponents, decreased the signaling of attack intentions, and induced attacks on females and anaesthetized opponents (Cordero et al., 2012; Márquez et al., 2013; Papilloud et al., 2018; Walker et al., 2018).”
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“There is also mounting evidence indicating that mitochondrial function and spare respiratory capacity might contribute to mechanisms of plasticity and stress resilience (Cherix et al., 2020; Choi et al., 2009; Filiou & Sandi, 2019; Papilloud et al., 2018; Picard et al., 2018).”
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Glucocorticoids and Aggression: A Tripartite Interaction
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Jin, Y., Fan, H., Shi, R., Song, G., Wu, X., Wang, D., Xia, B., Zhao, Z., Zhao, B., Liu, X., et al. (2024) · Food & Function · doi:10.1039/d3fo05078e · Cited by 10
Yin, X., Zhao, Y., Wang, S., Feng, H., He, X., Li, X., Liu, X., Lu, H., Wen, D., Shi, Y., et al. (2024) · Neuropharmacology · doi:10.1016/j.neuropharm.2024.109869 · Cited by 10
Hasler, G., Haynes, M., Müller, S. T., Tuura, R., Ritter, C., & Buchmann, A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.561464 · Cited by 7
“The amygdala has been found to act as a central structure in the association between peripubertal stress, adolescent brain development and later behavioral problems including social avoidance (30, 31).”
BackgroundSocial play in African savannah elephants may inform selection against aggression
Norscia, I., Hecker, M., Caselli, M., Collarini, E., Aldama, B. G., Santos, S. B., & Cordoni, G. (2024) · Current Zoology · doi:10.1093/cz/zoae009 · Cited by 7
“…dopamine, noradrenaline, glucocorticoid, and testosterone systems—involved in motivational, pleas-ure (reward system), and stress and fight-flight responses— play a prominent role in the variable modulation of social play (Meaney, 1988; Vanderschuren et al., 2016; Papilloud et al., 2018).”
Jelinek, J., Johne, M., Alam, M., Krauss, J. K., Kral, A., & Schwabe, K. (2024) · Current Research in Neurobiology · doi:10.1016/j.crneur.2024.100124 · Cited by 8
“Deficits in this behavior have been associated with neurodevelopmental disorders (Papilloud et al., 2018).”
BackgroundBorland, J. M. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105809 · Cited by 8
“The serotonin (Grieb et al., 2021), oxytocin (Olazabal and Young, 2006), vasopressin (Rigney et al., 2019), endocannabinoid (Papilloud et al., 2018) and the opioid system (Achterberg et al., 2019) are also essential neuropeptide and neurotransmitter systems in the nucleus accumbens that may display…”
Long term effects of peripubertal stress on the thalamic reticular nucleus of female and male mice
Alcaide, J., Gramuntell, Y., Klimczak, P., Bueno-Fernández, C., Garcia-Verellen, E., Guicciardini, C., Sandi, C., Castillo-Gómez, E., Crespo, C., Pérez-Rando, M., et al. (2024) · Neurobiology of Disease · doi:10.1016/j.nbd.2024.106642 · Cited by 7
“In this study we have employed a PPS protocol based on psychogenic factors, previously investigated in both male rats (M ´ arquez et al., 2013; Papilloud et al., 2018) and in male and female mice (Bueno-Fernandez al., 2021; Morat ´ o et al., 2022).”
BackgroundMethodResultInfluentialSelf-citationNuancing ‘Emotional’ Social Play: Does Play Behaviour Always Underlie a Positive Emotional State?
Cordoni, G., & Norscia, I. (2024) · Animals · doi:10.3390/ani14192769 · Cited by 9
Zutshi, I., Gupta, S., Zanoletti, O., Sandi, C., & Poirier, G. L. (2021) · Translational Psychiatry · doi:10.1038/s41398-021-01659-2 · Cited by 7
“The play behavior was performed on F1 male Wistar rats (Charles River), as previously reported [29].”
MethodInfluentialSelf-citationAnimal models built for women’s brain health: Progress and potential
Morrison, K. E. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100872 · Cited by 5
“For example, play behavior, which peaks around puberty, is an important social experience that facilitates adult cognitive and social skills in rats and mice (Papilloud et al., 2018; Schneider et al., 2016).”
BackgroundWalker, S. L., & Glasper, E. R. (2024) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2024.101162 · Cited by 3
Demuru, E., Montello, I., Guéry, J., Pellegrino, F., Levréro, F., & Norscia, I. (2025) · American Journal of Primatology · doi:10.1002/ajp.23723 · Cited by 2
Clark, G. B., Díez‐León, M., & Meagher, R. K. (2025) · Animal Welfare · doi:10.1017/awf.2024.71 · Cited by 2
“…of adaptation of cortico-sterone responses after repeated exposure to acute stressors, particularly if these stressors occur in adolescence – perhaps as a result of the greater ability of juveniles to adapt their behaviour as a stress-coping strategy (Sadler & Bailey 2016; Papilloud et al. 2018).”
The Biology of Glucocorticoids: Normal and Abnormal Aggression
Haller, J. (2020) · Springer eBooks · doi:10.1007/978-3-030-46331-1_5 · Cited by 1
Nuancing 'Emotional' Social Play: Does Play Behaviour Always Underlie a Positive Emotion?Preprint
Cordoni, G., & Norscia, I. (2024) · Preprints.org · doi:10.20944/preprints202407.1348.v1 · Cited by 1
Martins, G. W., Chagas, G. S., Patrício, F. C., Lira, A. D. O., Fragoso, J., Santos, A. B., & Leandro, C. G. (2020) · Behavioural Processes · doi:10.1016/j.beproc.2020.104151
Just, N. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.14.203067
“[26] Papilloud A, Guillot de Suduiraut I, Zanoletti O, Grosse J, Sandi C.”
BackgroundDistorted Circuitry in Violent Animals
Haller, J. (2020) · Springer eBooks · doi:10.1007/978-3-030-46331-1_8
Saha, S., & Saha, S. (2023) · Journal of the Turkish-German Gynecological Association · doi:10.4274/jtgga.galenos.2023.2022-12-4
“As the method of diagnosis of PCOS remains unclear in pre-pubertal and peri-pubertal girls (5,7), preliminary analyses will be repeated following the exclusion of trials in women aged ≤19 years (as peri-puberty is up to adolescence, i.e., age 19 (48,49).”
MethodKraatz, G., Xie, H. T. H., Long, H., & Walker, C. (2024) · Journal of Neuroendocrinology · doi:10.1111/jne.13483
“The current effect of LB on social play is consistent with previous studies showing that neonatal maternal separation 58 or peri-pubertal stress 59 can both increase play fighting behavior and lead to increased aggression in adulthood.”
Demuru, E., Collarini, E., Menon, A., Cesarano, G., Catinaud, J., Norscia, I., & Cordoni, G. (2024) · Animal Behaviour · doi:10.1016/j.anbehav.2024.11.020 · Cited by 1
Favoretto, C. A., Nguyen, A., Chacon, G. R., Roberts, A. J., Nadav, T., Ranjan, S., Bertotto, L. B., Cruz, F. C., & Zorrilla, E. P. (2025) · Frontiers in Neuroscience · doi:10.3389/fnins.2025.1568952
Poitras, M., Ouellette, É., Pellis, S. M., & Plamondon, H. (2025) · Behavioural Processes · doi:10.1016/j.beproc.2025.105301
Methylation and merriment: an exploration of epigenetic mechanisms underlying play behaviour
Malka, R. J., Arranz, M., & Baselga-Carretero, I. (2026) · Biological reviews/Biological reviews of the Cambridge Philosophical Society · doi:10.1002/brv.70142
“In domesticated rodents, social play occurs earlier when aggression is increased (Papilloud et al ., 2018; Tielbeek et al ., 2018).”
Metadata
- Authors
- Papilloud, A., Guillot de Suduiraut, I., Zanoletti, O., Grosse, J., & Sandi, C.
- Affiliations
- École Polytechnique Fédérale de Lausanne (CH)
- Corresponding author
- Sandi, Carmen
- Venue
- Translational Psychiatry
- Published
- 2018-08-15
- Volume
- 8
- Issue
- 1
- Pages
- 156-156
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC6093900
- OpenAlex
- W2886260261
- Cited by
- 38
- References
- 74
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 12 · 2023: 4 · 2022: 2 · 2021: 3 · 2020: 9 · 2019: 2
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (submittedVersion, cc-by)
- PubMed Central (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Funders
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (51NF40-158776)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Social Psychology › Bullying, Victimization, and Aggression
- Keywords
- play fighting, adolescent aggression, adult aggression, CB1 receptor, nucleus accumbens shell, brain energy metabolism, individual differences, early life stress, social behavior
- MeSH terms
- Aggression, Amygdala, Animals, Carrier Proteins, Energy Metabolism, Individuality, Male, Mitochondria, Nucleus Accumbens, Psychopathology, Reward, Stress, Psychological, Gene Expression, Rats, Wistar, Rats
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