Oxytocin neurons mediate the effect of social isolation via the VTA circuits
Open accessPublished version of a preprint
Abstract
Social interaction during adolescence strongly influences brain function and behavior, and the recent pandemic has emphasized the devastating effect of social distancing on mental health. While accumulating evidence has shown the importance of the reward system in encoding specific aspects of social interaction, the consequences of social isolation on the reward system and the development of social skills later in adulthood are still largely unknown. Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference. Behavioral changes were accompanied by the acute hyperexcitability of putative dopamine (pDA) neurons in the ventral tegmental area and long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex. Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus. These results demonstrate that social isolation in male mice has acute and long-lasting effects on social interaction and suggest that homeostatic adaptations mediate these effects within the reward circuit.
AI snapshot
Written from the paper’s full text.
TL;DR
One week of social isolation during adolescence in male mice increased social interaction but impaired social habituation and social novelty preference. These acute and long-lasting behavioral changes were mediated by PVN oxytocin neurons, VTA putative dopamine neuron hyperexcitability, and GluA2-lacking AMPARs at PFC-projecting VTA dopamine neurons.
Key findings
- Adolescent social isolation (P28–P35) increased social interaction versus group-housed controls (Mann-Whitney U=14, p=0.0052, n=10/group) without changing object exploration (p=0.2176), and also increased interaction with a former cage mate (t(13)=6.885, p<0.001).
- Isolated mice showed impaired social novelty preference: unlike grouped mice (t(15)=5.774, p<0.001), isolated mice spent similar time with familiar and unfamiliar conspecifics (t(15)=0.102, p=0.9201); they also failed to habituate across 4 days (isolated Day 1 vs Day 4, p=0.9094; grouped p=0.0087).
- Social isolation increased VTA putative dopamine neuron excitability (house condition main effect F(1,22)=8.016, p=0.0097) and PVN oxytocin neuron activity/density (cFos+ cells t(22)=2.510, p=0.0199; OXT+ cells p=0.0439; OXT+/cFos+ cells p=0.021). Chemogenetic inhibition of oxytocin neurons with CNO rescued social interaction (CNO treatment main effect F(1,28)=7.088, p=0.0127; CNO × housing p=0.0466).
- Long-lasting effects at adulthood included increased social interaction (t(18)=3.004, p=0.0076), blocked by CNO during isolation (F(2,19)=9.430, p=0.0014), and increased rectification index at excitatory inputs onto VTA dopamine neurons projecting to PFC (t(12)=3.545, p=0.004), but not NAc (p=0.7176); intra-VTA NASPM normalized social interaction in regrouped mice (NASPM × housing F(1,24)=6.099, p=0.021).
Methods
- Male wild-type and Oxt-hM4Di mice were used; adolescent isolation was single-housing from P28 to P35, with some mice regrouped until P60 for long-lasting experiments.
- Behavioral assays included direct free interaction, three-chamber sociability/social novelty, long and short habituation, novel object recognition, elevated plus maze, and social conditioned place preference.
- Neural methods included whole-cell patch-clamp recordings from VTA putative dopamine neurons and PVN-VTA projecting neurons, cFos/oxytocin/AVP immunofluorescence, retrograde CTB tracing from PFC/NAc/VTA, chemogenetic CNO treatment in drinking water, and intra-VTA NASPM infusion before behavior.
Limitations
- The paper explicitly states that only male mice were studied and that the lack of females limits whether the results apply to both sexes; it notes sex differences in oxytocin’s behavioral effects and calls for future studies in females.
- Evident from the text: some electrophysiology groups are small (e.g., AMPA/NMDA ratio n=5/group; several patch-clamp groups n=5–8), and behavioral scoring was manual, though experimenters were blinded.
- Evident from the text: the study focuses on one isolation duration and age window, so conclusions about other durations or developmental periods are not established here.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 60 cited sources checked · 0 supported · 0 flagged
- Findingown data
One week of social isolation during adolescence in male mice reduced social novelty preference.
“at the expense of social habituation and social novelty preference”
- Also stated in: § Results · hedged
“indicating that social isolation affects social novelty preference.”
Quote in the paperSubstantial claim - Also stated in: § Results · hedged
- Findingown data
One week of social isolation during adolescence in male mice impaired social habituation when the same juvenile conspecific was presented over four consecutive days.
“After social isolation, mice presented deficits in habituation when exposed to the same juvenile conspecific for four consecutive days (Figure 1J–N).”
- Also stated in: § Abstract · plain
“at the expense of social habituation and social novelty preference”
Quote in the paperSubstantial claim - Also stated in: § Abstract · plain
- Findingown data
One week of social isolation during adolescence (P28-P35) in male mice increased social interaction with a conspecific compared with group-housed controls.
“Here, we found that 1 week of social isolation during adolescence in male mice increased social interaction at the expense of social habituation and social novelty preference.”
- Also stated in: § Results · plain
“Isolated mice spent more time interacting with the conspecific than the grouped control mice (Figure 1C).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
Object exploration did not differ between socially isolated and grouped control mice.
“Conversely, object exploration did not differ between the two groups, indicating that social isolation preferentially affects social exploration (Figure 1B, D).”
- Also stated in: § Results · plain
“Time exploring object (Mann-Whitney U-test=33, p=0.2176, n=10 mice each group).”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
Chemogenetic inhibition of oxytocin neurons with CNO during social isolation prevented the increase in social interaction in isolated mice.
“we found an increase in interaction time in untreated isolated versus grouped mice, while no difference was observed between mice treated with CNO independent of housing (Figure 3N).”
Quote in the paperSubstantial claim
- Findingown data
After social isolation, mice did not show habituation deficits when exposed to the same juvenile conspecific for four consecutive trials on the same day.
“but not when exposed to the same juvenile conspecific for four consecutive trials on the same day (Figure 1—figure supplement 1I-M).”
Quote in the paperNot a substantial claim - Findingown data
Chemogenetic inhibition of oxytocin neurons with CNO during social isolation rescued pDA neuron excitability in the VTA of isolated mice.
“We observed the rescue of excitability in cells recorded from isolated mice treated with CNO but not isolated mice treated with vehicle (Figure 3I-L, Figure 3—figure supplement 1I-L).”
Quote in the paperSubstantial claim - Findingown data
In adulthood, object exploration was not affected in mice isolated during adolescence.
“but object exploration was not affected (Figure 4D).”
Quote in the paperNot a substantial claim - Findingown data
Novel object recognition did not differ between socially isolated and control mice.
“Novel object recognition (Figure 1—figure supplement 2A-F) and behavior in the EPM (Figure 1—figure supplement 2A, H-L) did not differ between the socially isolated and control mice.”
Quote in the paperNot a substantial claim - Findingown data
Social isolation increased the excitability of putative dopamine neurons in the ventral tegmental area.
“We observed increased excitability after social isolation without a change in the resting membrane potential (Figure 2B and D).”
Quote in the paperSubstantial claim - Findingown data
In adult isolated mice, sociability did not differ from controls.
“At the same time, object exploration (Figure 1—figure supplement 3B-D), sociability, and social novelty preference (Figure 1—figure supplement 3E-L) were no different.”
Quote in the paperSubstantial claim - Findingown data
In the three-chamber task, socially isolated mice spent the same amount of time interacting with familiar and unknown conspecifics, unlike control mice.
“in contrast to the control mice, the socially isolated mice spent the same amount of time interacting with familiar and unknown conspecifics (Figure 1I and – supplement 1 G, H)”
- Also stated in: § Results · plain
“Isolated ### Paired sample t-test, t(15)=0.102, p=0.9201.”
Quote in the paperSubstantial claim - Also stated in: § Results · plain
- Findingown data
Increased social interaction after adolescent social isolation was also observed when a former cage mate was presented as the social stimulus.
“Increased social interaction was also found when a former cage mate was presented as a social stimulus (Figure 1E, F).”
Quote in the paperNot a substantial claim - Findingown data
Inhibition of oxytocin neuron activity during social isolation was sufficient to block the long-lasting consequences of social isolation and restore social behavior.
“Remarkably, inhibition of oxytocin neuron activity during social isolation was sufficient to block the long-lasting consequences of social isolation and restore social behavior (Figure 4J–K).”
Quote in the paperSubstantial claim - Findingown data
Social isolation increased the number of OXT+/cFOS+ double-positive cells in the PVN.
“and an increase of OXT+/cFOS+ double-positive cells (Figure 3A and D) after social isolation.”
Quote in the paperSubstantial claim - Findingown data
In adulthood, mice isolated during adolescence and then regrouped showed increased social interaction compared with controls.
“We still observed increased social interaction in mice isolated during adolescence compared to the control group (Figure 4B and C)”
Quote in the paperSubstantial claim - Findingown data
Neuronal excitability in adulthood did not differ between isolated and control mice.
“Neuronal excitability in adulthood did not differ between isolated and control mice (Figure 4—figure supplement 2A-I)”
Quote in the paperSubstantial claim - Findingown data
In adulthood, there was no difference in the AMPAR/NMDAR ratio between control and isolated mice at excitatory inputs onto pDA neurons projecting to the PFC.
“While we observed no difference in the ratio of AMPAR- and NMDAR-mediated currents between control and isolated mice (Figure 5C and D)”
Quote in the paperNot a substantial claim - Findingown data
In adulthood, the rectification index was increased at excitatory inputs onto pDA neurons projecting to the PFC in isolated mice.
“we observed an increase in rectification index (RI) at excitatory inputs onto pDA neurons projecting to the PFC in isolated mice (Figure 5E and F).”
Quote in the paperSubstantial claim - Findingown data
In the three-chamber task, both socially isolated and grouped mice spent significantly more time investigating a juvenile conspecific over a novel object.
“We found that the socially isolated and grouped mice spent significantly more time investigating a juvenile conspecific over a novel object (Figure 1H and – supplement 1 D, E, F).”
Quote in the paperNot a substantial claim - Findingown data
Social isolation increased the density of oxytocin neurons in the PVN.
“we observed an increase in the density of oxytocin neurons in the PVN (Figure 3A, C, Figure 3—figure supplement 1D)”
Quote in the paperSubstantial claim - Findingown data
Adult mice isolated for 7 days (P53-P60) spent less time interacting with a conspecific than control mice.
“We found that isolated adult mice spent less time interacting with a conspecific than the control mice.”
Quote in the paperSubstantial claim - Findingown data
PVN neurons projecting to the VTA showed increased excitability after social isolation compared with controls.
“we performed patch-clamp recording from PVN neurons projecting to the VTA (PVN-VTA), and we observed increased excitability compared to that of the control group (Figure 3E–G).”
Quote in the paperSubstantial claim - Findingown data
Both socially isolated and grouped mice preferred the social chamber in the social conditioned place preference test.
“both groups of mice preferred the social chamber when they were subjected to social conditioned place preference (sCPP—Figure 1—figure supplement 2M-R).”
Quote in the paperNot a substantial claim - Findingown data
In adult isolated mice, social novelty preference did not differ from controls.
“At the same time, object exploration (Figure 1—figure supplement 3B-D), sociability, and social novelty preference (Figure 1—figure supplement 3E-L) were no different.”
Quote in the paperSubstantial claim - Findingown data
Seven days after social isolation, PVN neurons immunopositive for cFos increased.
“We observed an increase in PVN neurons immunopositive for cFos, suggesting increased activity (Figure 3A, B, Figure 3—figure supplement 1B).”
Quote in the paperSubstantial claim - Findingown data
Social isolation did not change the resting membrane potential of putative dopamine neurons in the ventral tegmental area.
“We observed increased excitability after social isolation without a change in the resting membrane potential (Figure 2B and D).”
Quote in the paperNot a substantial claim - Findingown data
Behavior in the elevated plus maze did not differ between socially isolated and control mice.
“Novel object recognition (Figure 1—figure supplement 2A-F) and behavior in the EPM (Figure 1—figure supplement 2A, H-L) did not differ between the socially isolated and control mice.”
Quote in the paperNot a substantial claim - Findingown data
In adult isolated mice, object exploration did not differ from controls.
“At the same time, object exploration (Figure 1—figure supplement 3B-D), sociability, and social novelty preference (Figure 1—figure supplement 3E-L) were no different.”
Quote in the paperSubstantial claim - Findingcitation
A brief 24-hour period of social isolation did not increase social interaction.
“it was not observed after a brief 24-hr period of social isolation, as expected from previous work (Matthews et al., 2016; Figure 1—figure supplement 1A, B).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matthews et al., 2016 source
Not checked in the free run.
- Findingown data
No differences between groups were observed in spontaneous inhibitory postsynaptic currents.
“Moreover, no differences between groups were observed in the spontaneous inhibitory postsynaptic currents (sIPSCs) (Figure 5—figure supplement 1L-P)”
Quote in the paperSubstantial claim - Findingown data
At the end of social isolation, the rectification index was higher in isolated mice compared with controls at excitatory inputs onto pDA neurons projecting to the PFC.
“we observed that RI was higher in isolated compared to the control group at excitatory inputs onto pDA neurons projecting to the PFC (Figure 5—figure supplement 1E-F).”
Quote in the paperSubstantial claim - Findingown data
In adulthood, there was no change in the AMPA/NMDA ratio or rectification index at excitatory inputs onto pDA neurons projecting to the NAc.
“No change in the AMPA/NMDA ratio or the RI was observed at excitatory inputs onto pDA neurons projecting to the NAc (Figure 5H–K).”
Quote in the paperNot a substantial claim - Findingown data
One week of social isolation during adolescence is sufficient to generate a rebound increase in social interaction during the free-interaction task in male mice, independently whether the stimulus is a former cage mate or a novel stimulus.
“Here, we show that 1 week of social isolation during adolescence is sufficient to generate a rebound increase in social interaction during the free-interaction task in male mice, independently whether the stimulus is a former cage mate or a novel stimulus.”
Quote in the paperSubstantial claim - Findingown data
Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus.
“Social isolation-dependent behavioral deficits and changes in neural activity and synaptic plasticity were reversed by chemogenetic inhibition of oxytocin neurons in the paraventricular nucleus of the hypothalamus.”
Quote in the paperSubstantial claim - Findingown data
At the end of social isolation, there was no change in the AMPA/NMDA ratio or rectification index at excitatory inputs onto pDA neurons projecting to the NAc.
“No change in the AMPA/NMDA ratio or the RI was observed at excitatory inputs onto pDA neurons projecting to the NAc (Figure 5—figure supplement 1G-K).”
Quote in the paperNot a substantial claim - Findingown data
At the end of social isolation, there was no difference in the AMPAR/NMDAR ratio between control and isolated mice at excitatory inputs onto pDA neurons projecting to the PFC.
“While we observed no difference in the ratio of AMPAR- and NMDAR-mediated currents between control and isolated mice (Figure 5—figure supplement 1B-D)”
Quote in the paperNot a substantial claim - Findingown data
RI was normalized when the activity of oxytocin neurons was chemogenetically reduced during social isolation.
“Notably, we observed that RI was normalized when the activity of the oxytocin neurons was chemogenetically reduced during social isolation (Figure 5M and N).”
Quote in the paperSubstantial claim - Findingown data
Inhibition of CP-AMPARs in the VTA was sufficient to normalize social interaction in the regrouped mice.
“While NASPM did not affect the interaction time in control mice, the inhibition of CP-AMPARs in the VTA was sufficient to normalize social interaction in the regrouped mice (Figure 6C).”
Quote in the paperSubstantial claim - Findingown data
NASPM did not affect the interaction time in control mice.
“While NASPM did not affect the interaction time in control mice, the inhibition of CP-AMPARs in the VTA was sufficient to normalize social interaction in the regrouped mice (Figure 6C).”
Quote in the paperSubstantial claim - Findingown data
Social isolation does not affect short social habituation.
“However, social isolation does not affect short social habituation, suggesting that isolation does not affect short-term social memory (Figure 7).”
Quote in the paperSubstantial claim - Findingown data
Prolonged activation of DA neurons induced by social isolation promoted the insertion of CP-AMPARs.
“Here, we show that prolonged activation of DA neurons induced by social isolation promoted the insertion of CP-AMPARs.”
Quote in the paperSubstantial claim - Findingown data
In vivo blockade of these receptors was sufficient to rescue social isolation-induced behavioral deficits.
“In vivo blockade of these receptors was sufficient to rescue social isolation-induced behavioral deficits.”
Quote in the paperSubstantial claim - Findingown data
Isolated mice spent more time interacting with a conspecific than control mice did 1 month after regrouping.
“Isolated mice spent more time interacting with a conspecific than control mice did 1 month after regrouping, indicating that the rebound increase in free/unrestrained social interaction in a long-lasting effect of isolation .”
Quote in the paperSubstantial claim - Interpretationown data
Social isolation preferentially affects social exploration rather than object exploration.
“Conversely, object exploration did not differ between the two groups, indicating that social isolation preferentially affects social exploration (Figure 1B, D).”
Quote in the paperSubstantial claim - Interpretationown data
Adolescence is a critical period for developing social behavioral skills.
“Altogether, these data indicate that adolescence is a critical period for developing social behavioral skills”
Quote in the paperSubstantial claim - Interpretationown data
The effect of oxytocin neuron excitability on social interaction is mediated by increased activity of pDA neurons within the VTA.
“and suggest that this effect is mediated by the increased activity of pDA neurons within the VTA.”
Quote in the paperSubstantial claim- Rests on an assumption: Oxytocin neurons in the paraventricular nucleus of the hypothalamus directly project to the ventral tegmental area and release oxytocin there.
- Interpretationown data
Social isolation does not impact the reinforcing properties of social interaction.
“Moreover, social isolation does not impact the reinforcing properties of the social interaction since both groups of mice preferred the social chamber when they were subjected to social conditioned place preference (sCPP—Figure 1—figure supplement 2M-R).”
Quote in the paperNot a substantial claim- Rests on an assumption: Social interaction is generally a rewarding experience with reinforcing properties.
- Interpretationown data
Increased social interaction after social isolation is a consequence of increased excitability of oxytocin neurons of the PVN.
“Altogether, the data presented here indicate that increased social interaction after social isolation is the consequence of the increased excitability of oxytocin neurons of the PVN”
Quote in the paperSubstantial claim - Interpretationown data
Oxytocin neurons play a role in regulating social craving after isolation.
“and support the possible role of oxytocin neurons in regulating social craving after isolation.”
Quote in the paperSubstantial claim - Interpretationown data
The long-lasting behavioral consequences of social isolation, although induced by neuronal excitability, are exerted by a different neuronal mechanism.
“suggesting that the long-lasting behavioral consequences of social isolation, although induced by neuronal excitability, are exerted by a different neuronal mechanism.”
Quote in the paperSubstantial claim - Interpretationown data
PVN neuronal activity increased after social isolation.
“We observed an increase in PVN neurons immunopositive for cFos, suggesting increased activity (Figure 3A, B, Figure 3—figure supplement 1B).”
Quote in the paperSubstantial claim - Interpretationown data
The duration of isolation is an essential factor in determining the behavioral consequences of social isolation.
“These data suggest that the duration of the isolation is an essential factor in determining the behavioral consequences of social isolation.”
Quote in the paperSubstantial claim - Interpretationown data
An isolation-dependent increase in social interaction occurs during adulthood.
“These data indicate that an isolation-dependent increase in social interaction occurs during adulthood”
Quote in the paperSubstantial claim - Interpretationown data
Social isolation affects social novelty preference.
“indicating that social isolation affects social novelty preference.”
Quote in the paperSubstantial claim - Interpretationown data
Acute social isolation during adolescence leads to a long-lasting increase in free/unrestrained social interaction during adulthood.
“These behavioral data indicate that acute social isolation during adolescence leads to a long-lasting increase in free/unrestrained social interaction during adulthood.”
Quote in the paperSubstantial claim - Interpretationown data
Social isolation does not affect short-term social memory.
“However, social isolation does not affect short social habituation, suggesting that isolation does not affect short-term social memory (Figure 7).”
Quote in the paperSubstantial claim - Interpretationown data
Social isolation leads to long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex.
“long-lasting expression of GluA2-lacking AMPARs at excitatory inputs onto pDA neurons that project to the prefrontal cortex.”
Quote in the paperSubstantial claim - Interpretationown data
Social isolation in male mice has acute and long-lasting effects on social interaction.
“These results demonstrate that social isolation in male mice has acute and long-lasting effects on social interaction”
Quote in the paperSubstantial claim - Interpretationown data
Synaptic scaling was not the consequence of changes in inhibitory transmission.
“suggesting that synaptic scaling was not the consequence of changes in inhibitory transmission.”
Quote in the paperNot a substantial claim - Premisecitation
In humans, the response of the ventral tegmental area to social cues after brief isolation is increased.
“in humans, the response of the VTA to social cues after brief isolation is increased (Tomova et al., 2020).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tomova et al., 2020 source
Not checked in the free run.
- Interpretationreasoning
Changes within VTA dopamine neurons may be the substrate for social craving caused by acute social isolation.
“These data suggest that changes within VTA DA neurons may be the substrate for social craving caused by acute social isolation.”
Quote in the paperSubstantial claim - Premisecitation
In rodents, 24 hours of social isolation does not change synaptic strength onto dopamine neurons of the ventral tegmental area.
“While in rodents, 24 hr of social isolation does not change synaptic strength onto DA neurons of the VTA (Matthews et al., 2016)”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Matthews et al., 2016 source
Not checked in the free run.
- Interpretationreasoning
Homeostatic adaptations mediate the effects of social isolation within the reward circuit.
“and suggest that homeostatic adaptations mediate these effects within the reward circuit.”
Quote in the paperSubstantial claim - Interpretationreasoning
GluA2-lacking AMPARs are critical therapeutic targets for treating maladaptive motivated behavior.
“Taken together, all these findings indicate that GluA2-lacking AMPARs are critical therapeutic targets for treating maladaptive motivated behavior and suggest that inhibitors of these receptors may counteract the negative consequences of social isolation.”
Quote in the paperSubstantial claim - Premisecitation
Human exposure to social cues after acute isolation evokes activity in the VTA.
“It has been shown that human exposure to social cues after acute isolation evokes activity in the VTA (Tomova et al., 2020), suggesting that while DA neurons within the DRN mediate the loneliness-like brain state induced by social isolation, DA neurons in the VTA mediate social craving.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tomova et al., 2020 source
Not checked in the free run.
- Interpretationreasoning
Oxytocin neurons could represent the neural signature of social craving in male mice.
“Taken together, these data suggest that oxytocin neurons could represent the neural signature of social craving in male mice.”
Quote in the paperSubstantial claim - Interpretationown data
The rebound increase in free/unrestrained social interaction is a long-lasting effect of isolation.
“Isolated mice spent more time interacting with a conspecific than control mice did 1 month after regrouping, indicating that the rebound increase in free/unrestrained social interaction in a long-lasting effect of isolation .”
Quote in the paperSubstantial claim - Interpretationown data
One week of isolation during adolescence is sufficient to increase the overall excitability of neurons within the mesocorticolimbic system.
“Our data indicate that 1 week of isolation during adolescence is sufficient to increase the overall excitability of neurons within the mesocorticolimbic system.”
Quote in the paperSubstantial claim - Premisecitation
Restoration of oxytocin signaling in the VTA in an autism spectrum disorder-related mouse model was sufficient to rescue social novelty responses.
“Furthermore, restoration of oxytocin signaling in the VTA in an autism spectrum disorder-related mouse model was sufficient to rescue social novelty responses (Hörnberg et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hörnberg et al., 2020 source
Not checked in the free run.
- May combine two claims. 29
- Classified as probably not a substantial claim. 37
May combine two claims.
Findingown dataSociability, social novelty preference, and social habituation were similar between grouped and regrouped mice.
“Sociability, social novelty preference (Figure 4—figure supplement 1A-I), and social habituation were similar between grouped and regrouped mice (Figure 4E, I)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataSocial isolation did not affect the number of vasopressin-positive cells, AVP+/cFOS+ cells, or OXT+/AVP+ cells.
“On the contrary, social isolation does not affect the number of vasopressin (AVP) positive cells nor the AVP+/cFOS+ or OXT+/AVP+ (Figure 3—figure supplement 1C, E, H)”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataDuring the first interaction, regrouped mice interacted more than grouped mice.
“although during the first interaction, regrouped mice interacted more (Figure 4F).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn VTA-pDA:mPFC projecting neurons, there was a significant main effect of CNO treatment (F(1,23)=11.19, p=0.0028), a significant main effect of house condition (F(1,23)=5.459, p=0.0285), and a significant interaction (F(1,23)=11.22, p=0.028) on RI.
“RI of VTA-pDA:mPFC projecting neurons (Two-way ANOVA followed by Tukey’s multiple comparisons test, CNO treatment main effect F(1, 23)=11.19, p=0.0028, House condition main effect F(1, 23)=5.459, p=0.0285, CNO treatment × Hous condition F(1, 23)=11.22, p=0.028, Grouped n=8, Grouped CNO n=7, Regrouped n=7, Regrouped CNO n=5 from two mice each group).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataIn social interaction time, there was a significant main effect of NASPM treatment (F(1,24)=13.78, p=0.0011), no significant main effect of house condition (F(1,24)=2.626, p=0.1182), and a significant interaction (F(1,24)=6.099, p=0.021).
“Social interaction time (Two-way ANOVA followed by Tukey’s multiple comparisons test, NASPM treatment main effect F (1, 24)=13.78, p=0.0011, House condition main effect F(1, 24)=2.626, p=0.1182, NASPM × House condition F(1, 24)=6.099, p=0.021, Grouped Veh n=6, Grouped NASPM n=7, Regrouped Veh n=8, Regropued NASPM n=7).”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe increase in interaction is accompanied by deficits in social novelty preference and social habituation across days.
“The increase in interaction is accompanied by deficits in social novelty preference and social habituation across days.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataSocial isolation during adolescence increases social interaction at the expense of impaired social novelty preference and altered habituation to interact with a familiar conspecific.
“and that social isolation during this period increases social interaction at the expense of an impaired social novelty preference and altered habituation to interact with a familiar conspecific.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataSocial isolation induces an alteration of oxytocin rather than a modification of cell identity.
“suggesting that social isolation induces an alteration of oxytocin rather than a modification of the cell identity.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim. May combine two claims.
PremisecitationDopamine neurons of the ventral tegmental area are necessary and sufficient to promote social interaction.
“Recent studies have highlighted the necessity and sufficiency of dopamine (DA) neurons of the ventral tegmental area (VTA) to promote social interaction (Gunaydin et al., 2014; Solié et al., 2022).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationOxytocin in the VTA activates oxytocin receptors on dopamine neurons and regulates their activity, suggesting that oxytocin in the VTA gates social reward.
“Oxytocin in the VTA activates oxytocin receptors on DA neurons regulates their activity, suggesting that oxytocin in the VTA gates social reward (Hung et al., 2017; Tang et al., 2014; Xiao et al., 2017).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
Interpretationown dataSocial isolation during adolescence leads to long-lasting effects in free/unrestrained social interaction accompanied by oxytocin neuron-dependent changes in synaptic transmission at excitatory inputs onto pDA neurons projecting to the PFC.
“These data indicate that social isolation during adolescence leads to long-lasting effects in free/unrestrained social interaction accompanied by oxytocin neuron-dependent changes in synaptic transmission at excitatory inputs onto pDA neurons projecting to the PFC.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn rodents, depending on the duration of juvenile social isolation, increased or decreased sociability in adulthood has been reported, suggesting that adolescence is a sensitive period for establishing social behavior later in life.
“In rodents, depending on the duration of juvenile social isolation, increased or decreased sociability in adulthood has been reported, suggesting that adolescence is a sensitive period for establishing social behavior later in life (Yamamuro et al., 2020; Yamamuro et al., 2018; Makinodan et al., 2012; Rivera-Irizarry et al., 2020).”
Quote in the paperNot a substantial claim0 of 3 sources checkedMay combine two claims.
Interpretationown dataThe increased activity of oxytocin neurons during social interaction induces synaptic scaling exerted by the presence of CP-AMPARs and these receptors are responsible for increased social interaction during adulthood.
“The data presented here show that the increased activity of oxytocin neurons during social interaction induces synaptic scaling exerted by the presence of CP-AMPARs and that these receptors are responsible for increased social interaction during adulthood.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationThe presence of a conspecific activates the oxytocin system, increases oxytocin release, activates dopamine neurons of the VTA, and promotes the initiation and maintenance of social interaction.
“Indeed, the presence of a conspecific activates the oxytocin system, which increases oxytocin release, activates DA neurons of the VTA, and promotes the initiation and maintenance of social interaction (Resendez et al., 2020; Oettl et al., 2016).”
Quote in the paperSubstantial claim0 of 2 sources checkedMay combine two claims.
PremisecitationBrief periods of acute social isolation activate midbrain regions in humans and increase dopamine neuron activity within the dorsal raphe nucleus in mice.
“Brief periods of acute social isolation have been reported to activate midbrain regions in humans (Tomova et al., 2020) and increase DA neurons’ activity within the dorsal Raphe nucleus (DRN) in mice (Matthews et al., 2016).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationShort-term isolation has increased social interaction in rats.
“For example, short-term isolation has increased social interaction in rats (Niesink and van Ree, 1982).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Niesink and van Ree, 1982
Not checked in the free run.
May combine two claims.
Interpretationown dataThe activity of oxytocin neurons within the PVN is causally linked to neuronal excitability within the reward system and the behavioral consequences of social isolation.
“We next investigated the underlying mechanisms and found that the activity of oxytocin neurons within the PVN is causally linked to neuronal excitability within the reward system and the behavioral consequences of social isolation.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAdolescence is a critical period for social interaction and the emergence of psychiatric diseases.
“Indeed, adolescence is a critical period for not only social interaction (Larsen and Luna, 2018; ) but also the emergence of psychiatric diseases (Orben et al., 2020; Marco et al., 2011), and social isolation during adolescence can exacerbate mental health problems (Larsen and Luna, 2018; Almeida et al., 2021; ; Graf et al., 2021; Andersen, 2021).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationAcute social isolation during adulthood changes the synaptic strength at excitatory inputs onto DA neurons of the DRN in rodents, leaving synaptic transmission onto DA neurons of the VTA unaltered.
“Remarkably, acute social isolation during adulthood changes the synaptic strength at excitatory inputs onto DA neurons of the DRN in rodents, leaving synaptic transmission onto DA neurons of the VTA unaltered (Matthews et al., 2016).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Matthews et al., 2016 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSocial isolation during adolescence can exacerbate mental health problems.
“Indeed, adolescence is a critical period for not only social interaction (Larsen and Luna, 2018; ) but also the emergence of psychiatric diseases (Orben et al., 2020; Marco et al., 2011), and social isolation during adolescence can exacerbate mental health problems (Larsen and Luna, 2018; Almeida et al., 2021; ; Graf et al., 2021; Andersen, 2021).”
Quote in the paperNot a substantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe lack of female in the present study poses a limit in our results since we do not know whether our results apply to both sexes.
“The lack of female in the present study poses a limit in our results since we do not know whether our results apply to both sexes.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe adverse effects of social isolation are particularly apparent for adolescents.
“The adverse effects of social isolation are particularly apparent for adolescents (Almeida et al., 2021; Orben et al., 2020).”
Quote in the paperNot a substantial claim0 of 2 sources checkedClassified as probably not a substantial claim.
PremisecitationDuring adolescence, social and cognitive skills depend on peer-to-peer interactions.
“During adolescence, social and cognitive skills depend on peer-to-peer interactions (Vanderschuren et al., 1997; Baarendse et al., 2013), and acute social isolation in rodents is sufficient to cause behavioral abnormalities, including increased vulnerability to drug addiction and depressive-like behavior, later in life (Lampert et al., 2017; Takatsu-Coleman et al., 2013; Whitaker et al., 2013).”
Quote in the paperSubstantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSocial isolation is an adverse experience across social species with long-lasting behavioral and physiological consequences.
“Social isolation is an adverse experience across social species with long-lasting behavioral and physiological consequences (Cacioppo et al., 2014).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Cacioppo et al., 2014 source
Not checked in the free run.
May combine two claims.
Interpretationown dataAdolescence is a critical period for the establishment of social behavior and isolation during this period alters sociability during adulthood.
“Although the duration of social isolation can explain the differences at the behavioral level between the two studies, these data show that adolescence is a critical period for the establishment of social behavior and that isolation during this period alters sociability during adulthood.”
Quote in the paperSubstantial claimClassified as probably not a substantial claim.
PremisecitationAcute social isolation in rodents is sufficient to cause behavioral abnormalities, including increased vulnerability to drug addiction and depressive-like behavior, later in life.
“During adolescence, social and cognitive skills depend on peer-to-peer interactions (Vanderschuren et al., 1997; Baarendse et al., 2013), and acute social isolation in rodents is sufficient to cause behavioral abnormalities, including increased vulnerability to drug addiction and depressive-like behavior, later in life (Lampert et al., 2017; Takatsu-Coleman et al., 2013; Whitaker et al., 2013).”
Quote in the paperSubstantial claim0 of 3 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenThe experimental mice were randomly assigned to the different groups.
“The experimental mice were randomly assigned to the different groups.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationDA neurons in the VTA play a role in social behavior.
“Previous studies have indicated the role of DA neurons in the VTA in social behavior (Gunaydin et al., 2014; Bariselli et al., 2018; Bariselli et al., 2016b) and shown that chronic isolation alters DA levels in the NAc (Hall et al., 1998; ).”
Quote in the paperSubstantial claim0 of 3 sources checkedMay combine two claims.
InterpretationreasoningDuring adulthood, increased social interaction is accompanied and causally linked to the increase in GluA2-lacking AMPARs at excitatory inputs onto pDA neurons projecting to the PFC.
“During adulthood, increased social interaction is accompanied and causally linked to the increase in GluA2-lacking AMPARs at excitatory inputs onto pDA neurons projecting to the PFC.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChronic isolation alters DA levels in the NAc.
“Previous studies have indicated the role of DA neurons in the VTA in social behavior (Gunaydin et al., 2014; Bariselli et al., 2018; Bariselli et al., 2016b) and shown that chronic isolation alters DA levels in the NAc (Hall et al., 1998; ).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Hall et al., 1998 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThese data support the hypothesis that social interaction is a need and that the absence of social cues generates a craving response like that caused by food cues after fasting.
“These data support the hypothesis that social interaction is a need and that the absence of social cues generates a craving response like that caused by food cues after fasting (Tomova et al., 2020).”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Tomova et al., 2020 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationEstrogens play a fundamental role in the sexually dimorphic formation of brain structures by modulating neural circuits that control sex-specific behavior, including social interaction.
“Indeed, estrogens play a fundamental role in the sexually dimorphic formation of brain structures by modulating neural circuits that control sex-specific behavior, including social interaction (Ogawa et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ogawa et al., 2020 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThese receptors are inserted at excitatory synapses after exposure to addictive drugs and have been proposed to mediate the incubation of drug craving.
“These receptors are inserted at excitatory synapses after exposure to addictive drugs (Bellone and Lüscher, 2006) and have been proposed to mediate the incubation of drug craving (Conrad et al., 2008).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Bellone and Lüscher, 2006
Not checked in the free run.
- cites Conrad et al., 2008 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationGluA2-lacking AMPARs are CP ionotropic receptors with larger single-channel conductance and can undergo voltage-dependent blockade by polyamines.
“GluA2-lacking AMPARs are CP ionotropic receptors with larger single-channel conductance and can undergo voltage-dependent blockade by polyamines (Twomey et al., 2018; Man, 2011).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe presence of these receptors changes the rules for the induction of plasticity and mediates in vivo synaptic scaling.
“Furthermore, the presence of these receptors changes the rules for the induction of plasticity (Mameli et al., 2011) and mediates in vivo synaptic scaling (Garcia-Bereguiain et al., 2013).”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationStress induces the insertion of these receptors, and local blockade of GluA2-lacking AMPARs attenuates stress-induced behavioral changes in rodents.
“Moreover, it has also been shown that stress induces the insertion of these receptors, and local blockade of GluA2-lacking AMPARs was shown to attenuate stress-induced behavioral changes in rodents (Kuniishi et al., 2020; Yi et al., 2017).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Kuniishi et al., 2020 source
Not checked in the free run.
- cites Yi et al., 2017
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationGonadal steroids regulate Oxt activity, and estrogen seems to have higher impact on the Oxt system.
“Gonadal steroids regulate Oxt activity, and among them, estrogen seems to have higher impact on the Oxt system (Richard and Zingg, 1990; Miller and Caldwell, 2015; Gimpl and Fahrenholz, 2001).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Richard and Zingg, 1990
Not checked in the free run.
- cites Miller and Caldwell, 2015
Not checked in the free run.
- cites Gimpl and Fahrenholz, 2001 source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductnone givenFor VTA excitability, pDA neurons were identified according to their position (medially to the medial terminal nucleus of the accessory optic tract), morphology (large soma), and cell capacitance (> 28 pF).
“For VTA excitability, pDA neurons were identified accordingly to their position (medially to the medial terminal nucleus of the accessory optic tract), morphology (large soma), and cell capacitance (> 28 pF, see Figure 5—figure supplement 2).”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationSex differences in oxytocin's behavioral effects can be found in rodents.
“Although sex differences in oxytocin and oxytocin receptor distribution have not been reported, sex differences in oxytocin’s behavioral effects can be found in rodents (Miller and Caldwell, 2015; Tamborski et al., 2016; Hammock and Levitt, 2013).”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites Miller and Caldwell, 2015
Not checked in the free run.
- cites Tamborski et al., 2016 source
Not checked in the free run.
- cites Hammock and Levitt, 2013
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAccess resistance (10-30 MΩ) was monitored by a hyperpolarizing step of -4 mV at each sweep, every 10 s.
“Access resistance (10–30 MΩ) was monitored by a hyperpolarizing step of –4 mV at each sweep, every 10 s.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationNeonatal oxytocin treatment modifies the development of social behavior resulting in a reduction of alloparenting, and treatment during puberty reduces social play behavior, both effects occurring only in female.
“Indeed, neonatal oxytocin treatment modifies the development of social behavior resulting in a reduction of alloparenting (Mogi et al., 2014) and treatment during puberty reduces social play behavior (Bredewold et al., 2014). Both these effects occur only in female.”
Quote in the paperNot a substantial claim0 of 2 sources checkedProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoningThe AMPA/NMDA ratio values may be underestimated because the ratio was calculated with spermine in the pipette.
“The ratio values may be underestimated since it was calculated with spermine in the pipette.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductnone givenPutative VTA-DA neurons were identified by larger soma compared to other cells and a capacitance >28 pF.
“Putative VTA-DA neurons were identified for larger soma compared to the other cells and a capacitance >28 pF.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationIn the brain there are sex differences in tissue structures and dimorphic nuclei exhibiting morphological sex differences are considered as the structural basis for generating sex differences in brain functions.
“In the brain there are sex differences in the tissue structures and the dimorphic nuclei exhibiting morphological sex differences are considered as the structural basis for generating sex differences in brain functions (Ogawa et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Ogawa et al., 2020 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenData were excluded when the access resistance changed >20%.
“Data were excluded when the resistance changed >20%.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenCells with capacitance lower than 27 pF were not considered putative VTA-DA neurons.
“Cells with capacitance lower than 27 pF were not considered putative-DA neurons (Figure 5—figure supplement 2).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationThe release of oxytocin in the VTA increases DA neuron firing within the VTA.
“Previously, the release of oxytocin in the VTA was shown to increase DA neuron firing within the VTA (Xiao et al., 2017).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Xiao et al., 2017 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationTwo weeks of social isolation after weaning altered the pathway from the medial PFC to the posterior paraventricular thalamus, leading to decreased sociability in adult mice.
“Recently, it was reported that 2 weeks of social isolation after weaning altered the pathway from the medial PFC to the posterior paraventricular thalamus, leading to decreased sociability in adult mice (Yamamuro et al., 2020).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Yamamuro et al., 2020 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationcitationDA neurons within the DRN mediate the loneliness-like brain state induced by social isolation, while DA neurons in the VTA mediate social craving.
“It has been shown that human exposure to social cues after acute isolation evokes activity in the VTA (Tomova et al., 2020), suggesting that while DA neurons within the DRN mediate the loneliness-like brain state induced by social isolation, DA neurons in the VTA mediate social craving.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Tomova et al., 2020 source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll experimenters were blinded to perform behavioral manual scores and analyses.
“All the experimenters were blinded to perform behavioral manual scores and analyses.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenNonparametric tests were also used when unequal variance was present.
“Nonparametric tests were also used when unequal variance was present.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationStatistical outliers were identified with the ROUT method (Q=1) and excluded from the analysis.
“Statistical outliers were identified with the ROUT method (Motulsky and Brown, 2006) (Q=1) and excluded from the analysis.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Motulsky and Brown, 2006
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenThe normality of sample distributions was assessed with the Shapiro-Wilk criterion, and when normality was violated nonparametric tests were used.
“The normality of sample distributions was assessed with the Shapiro-Wilk criterion, and when violated nonparametric tests were used.”
Quote in the paperNot a substantial claim
The paper relies on this without support.
The role of oxytocin neurons in the behavioral consequences of social isolation is largely unknown.
“the role of oxytocin neurons in the behavioral consequences of social isolation remains largely unknown.”
The paper relies on this without support.
Social interaction is generally a rewarding experience with reinforcing properties.
“Social interaction is generally a rewarding experience with reinforcing properties.”
The paper relies on this without support.
Oxytocin neurons in the paraventricular nucleus of the hypothalamus directly project to the ventral tegmental area and release oxytocin there.
“Oxytocin is a neuropeptide released by neurons within the paraventricular nucleus (PVN) of the hypothalamus that directly projects to the VTA.”
The paper relies on this without support.
A short period of deprivation from conspecific interaction may also trigger aversive consequences.
“Although anxiety, depression, and obsessive-compulsive behavior generally emerge after prolonged social isolation (Teo et al., 2013; Pietrabissa and Simpson, 2020; Leigh-Hunt et al., 2017), it is evident that a short period of deprivation from conspecific interaction may also trigger aversive consequences.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Chronic psychosocial stress, specifically social isolation during adolescence, led to increased social interaction but impaired social recognition in adult male mice compared with those housed in groups.
“A recent study found that chronic psychosocial stress, specifically social isolation during adoles cence, led to increased social interaction but impaired social recognition in adult male mice compared with those housed in groups (Musardo et al., 2022).”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Musardo et al., 2022
The Results (Figure 4) report increased social interaction in adulthood after seven days of adolescent isolation. They also say social novelty preference in adulthood was similar between previously isolated and group-housed mice; the deficit appeared immediately after isolation during adolescence (Results, Figure 1). The paper describes the isolation as acute, not chronic. (LLM, conf=0.90)
Experimental — accuracy not yet measuredBy suppressing PVN-OXT neurons using chemogenetics, social interaction and VTA-DA neuron excitability were normalized in isolated mice.
“By suppressing PVN-OXT neurons using chemogenetics, social interaction and VTA-DA neuron excitability were normalized in isolated mice.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Musardo et al., 2022
Electrophysiological recordings showed increased excitability in PVN neurons projecting to the VTA.
“Additionally, electrophysiological recordings showed increased excitability in PVN neurons projecting to the VTA.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Musardo et al., 2022
These behavioural changes were associated with heightened activity and quantity of OXT neurons in the PVN.
“These behavioural changes were associated with height ened activity and quantity of OXT neurons in the PVN.”
From Convergence of oxytocin and dopamine signalling in neuronal circuits: Insights into the neurobiology of social interactions across species (2024) · cites this paper as Musardo et al., 2022
One week of social isolation during adolescence resulted in increased excitability of mPFC-projecting VTA DA neurons and increased social interaction but decreased social novelty preference.
“1 week of social isolation during adolescence resulted in increased excitability of mPFC-projecting VTA DA neurons and increased social interaction but decreased social novelty preference [155].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [155]
Acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC, whereas chronic stressors appear to lead to a hypodopaminergic state.
“Thus, acute stress may promote social interactions at least in part via upregulation of DA input activity in the mPFC [155], whereas chronic stressors appear to lead to a hypodopaminergic state [162].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [155]
These neural and behavioral adaptations were reversed via chemogenetic inhibition of OXT neurons in the PVN.
“These neural and behavioral adaptations were reversed via chemogenetic inhibition of OXT neurons in the PVN [155].”
From Neural circuits regulating prosocial behaviors (2023) · cites this paper as [155]
Statistics that don’t add up
Each reported p-value recomputed from its test statistic and degrees of freedom.
Inconsistent p-value: F(2, 60)=9.487, p > .001
MinorThe paper reports p > .001 here; recomputing from the test statistic and its degrees of freedom gives p < .001. The check cannot tell whether the statistic or the p-value is the misprint.
Reported p > .001 · recomputed p < .001
“F(2, 60)=9.487, p>0.001”
Inconsistent p-value: F(6, 180)=2.828, p = .018
MinorThe paper reports p = .018 here; recomputing from the test statistic and its degrees of freedom gives p = .012. The check cannot tell whether the statistic or the p-value is the misprint.
Reported p = .018 · recomputed p = .012
“F(6, 180)=2.828, p=0.018”
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(2, 60) = 9.487reported p > .001 · recomputed p < .001
“F(2, 60)=9.487, p > .001”
- Doesn’t add upF(6, 180) = 2.828reported p = .018 · recomputed p = .012
“F(6, 180)=2.828, p = .018”
- Consistentt(13) = 6.885reported p < .001 · recomputed p < .001
“t(13)=6.885, p < .001”
- Consistentt(15) = 5.975reported p < .001 · recomputed p < .001
“t(15)=5.975, p < .001”
- ConsistentF(1, 30) = 51.47reported p < .001 · recomputed p < .001
“F(1, 30)=51.47, p < .001”
- ConsistentF(1, 30) = 3.935reported p = .0565 · recomputed p = .057
“F(1, 30)=3.935, p = .0565”
- Consistentt(15) = 5.774reported p < .001 · recomputed p < .001
“t(15)=5.774, p < .001”
- Consistentt(15) = 0.102reported p = .9201 · recomputed p = .920
“t(15)=0.102, p = .9201”
- ConsistentF(1, 30) = 9.251reported p = .0049 · recomputed p = .005
“F(1, 30)=9.251, p = .0049”
- ConsistentF(1, 30) = 1.164reported p = .2892 · recomputed p = .289
“F(1, 30)=1.164, p = .2892”
- ConsistentF(1, 30) = 8.215reported p = .0075 · recomputed p = .008
“F(1, 30)=8.215, p = .0075”
- Consistentt(10) = 3.076reported p = .0117 · recomputed p = .012
“t(10)=3.076, p = .0117”
- ConsistentF(2.215, 22.15) = 6.775reported p = .0041 · recomputed p = .004
“F(2.215, 22.15)=6.775, p = .0041”
- ConsistentF(1, 10) = 1.455reported p = .2555 · recomputed p = .255
“F(1, 10)=1.455, p = .2555”
- ConsistentF(3, 30) = 4.349reported p = .0117 · recomputed p = .012
“F(3, 30)=4.349, p = .0117”
- Consistentt(5) = 5.706reported p = .0023 · recomputed p = .002
“t(5)=5.706, p = .0023”
- Consistentt(5) = 0.6552reported p = .5413 · recomputed p = .541
“t(5)=0.6552, p = .5413”
- ConsistentF(6, 132) = 2.23reported p = .044 · recomputed p = .044
“F(6, 132)=2.230, p = .044”
- ConsistentF(2.31, 50.82) = 36.65reported p < .001 · recomputed p < .001
“F(2.310, 50.82)=36.65, p < .001”
- ConsistentF(1, 22) = 8.016reported p = .0097 · recomputed p = .010
“F(1, 22)=8.016, p = .0097”
- Consistentt(22) = 2.51reported p = .0199 · recomputed p = .020
“t(22)=2.510, p = .0199”
- Consistentt(22) = 3.491reported p = .021 · recomputed p = .002
“t(22)=3.491, p = .021”
The paper states a correction for multiple tests
- ConsistentF(1, 30) = 7.306reported p = .0112 · recomputed p = .011
“F(1, 30)=7.306, p = .0112”
- ConsistentF(1.857, 55.71) = 30.47reported p < .001 · recomputed p < .001
“F(1.857, 55.71)=30.47, p < .001”
- ConsistentF(1.962, 98.08) = 114.8reported p < .0001 · recomputed p < .001
“F(1.962, 98.08)=114.8, p < .0001”
- ConsistentF(1, 50) = 3.456reported p = .0689 · recomputed p = .069
“F(1, 50)=3.456, p = .0689”
- ConsistentF(1, 50) = 5.826reported p = .0195 · recomputed p = .019
“F(1, 50)=5.826, p = .0195”
- ConsistentF(6, 300) = 1.866reported p = .0865 · recomputed p = .086
“F(6, 300)=1.866, p = .0865”
- ConsistentF(6, 300) = 3.806reported p = .0011 · recomputed p = .001
“F(6, 300)=3.806, p = .0011”
- ConsistentF(1, 50) = 2.293reported p = .1363 · recomputed p = .136
“F(1, 50)=2.293, p = .1363”
- ConsistentF(6, 300) = 3.459reported p = .0026 · recomputed p = .003
“F(6, 300)=3.459, p = .0026”
- ConsistentF(1, 50) = 0.8745reported p = .3542 · recomputed p = .354
“F(1, 50)=0.8745, p = .3542”
- ConsistentF(1, 50) = 1.956reported p = .1681 · recomputed p = .168
“F(1, 50)=1.956, p = .1681”
- ConsistentF(1, 50) = 3.531reported p = .0661 · recomputed p = .066
“F(1, 50)=3.531, p = .0661”
- ConsistentF(1, 28) = 7.088reported p = .0127 · recomputed p = .013
“F(1, 28)=7.088, p = .0127”
- ConsistentF(1, 28) = 9.94reported p = .0038 · recomputed p = .004
“F(1, 28)=9.940, p = .0038”
- ConsistentF(1, 28) = 4.334reported p = .0466 · recomputed p = .047
“F(1 ,28)=4.334, p = .0466”
- Consistentt(18) = 3.004reported p = .0076 · recomputed p = .008
“t(18)=3.004, p = .0076”
- Consistentt(18) = 3.3717reported p = .7144 · recomputed p = .003
“t(18)=3.3717, p = .7144”
The paper states a correction for multiple tests
- Consistentt(14) = 3.553reported p = .0032 · recomputed p = .003
“t(14)=3.553, p = .0032”
- ConsistentF(3, 42) = 2.607reported p = .064 · recomputed p = .064
“F(3, 42)=2.607, p = .064”
- ConsistentF(2.84, 39.76) = 32.66reported p < .001 · recomputed p < .001
“F(2.840, 39.76)=32.66, p < .001”
- ConsistentF(1, 14) = 8.24reported p = .0123 · recomputed p = .012
“F(1, 14)=8.240, p = .0123”
- Consistentt(7) = 3.923reported p = .0057 · recomputed p = .006
“t(7)=3.923, p = .0057”
- Consistentt(7) = 7.621reported p < .001 · recomputed p < .001
“t(7)=7.621, p < .001”
- ConsistentF(2, 19) = 9.43reported p = .0014 · recomputed p = .001
“F(2, 19)=9.430, p = .0014”
- Consistentt(8) = 0.0754reported p = .9417 · recomputed p = .942
“t(8)=0.07544, p = .9417”
- Consistentt(12) = 3.545reported p = .004 · recomputed p = .004
“t(12)=3.545, p = .004”
- Consistentt(10) = 0.372reported p = .7176 · recomputed p = .718
“t(10)=0.3720, p = .7176”
- ConsistentF(1, 23) = 11.19reported p = .0028 · recomputed p = .003
“F(1, 23)=11.19, p = .0028”
- ConsistentF(1, 23) = 5.459reported p = .0285 · recomputed p = .029
“F(1, 23)=5.459, p = .0285”
- ConsistentF(1, 23) = 11.22reported p = .028 · recomputed p = .003
“F(1, 23)=11.22, p = .028”
The paper states a correction for multiple tests
- ConsistentF(1, 24) = 13.78reported p = .0011 · recomputed p = .001
“F (1, 24)=13.78, p = .0011”
- ConsistentF(1, 24) = 2.626reported p = .1182 · recomputed p = .118
“F(1, 24)=2.626, p = .1182”
- ConsistentF(1, 24) = 6.099reported p = .021 · recomputed p = .021
“F(1, 24)=6.099, p = .021”
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.
Object-exploration test statistic conflicts with its reported p-value
MinorFor a two-sided t-test with 18 degrees of freedom, t=3.3717 implies a p-value of about 0.0034, not 0.7144. The reported p-value supports the paper's conclusion that object exploration was unaffected, whereas the reported t-statistic does not.
“t(18)=3.3717”
“p=0.7144”
OXT/cFos t-statistic conflicts with its reported p-value
MinorFor a two-sided t-test with 22 degrees of freedom, t=3.491 implies a p-value of about 0.0021, not 0.021.
“t(22)=3.491”
“p=0.021”
Reported degrees of freedom conflict with group sizes in Figure 5F
MinorFor the stated unpaired t-test with eight observations in each group, the degrees of freedom would be 14, not 12.
“Unpaired samples t-test, t(12)=3.545”
“Grouped n=8, Isolated n=8”
Cites
The oxytocin receptor system: structure, function, and regulation
Gimpl, G., & Fahrenholz, F. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.629 · Cited by 3,089 · see citing works
Leigh-Hunt, N., Bagguley, D., Bash, K., Turner, V., Turnbull, S., Valtorta, N., & Caan, W. (2017) · Public Health · doi:10.1016/j.puhe.2017.07.035 · Cited by 2,158 · see citing works
Motulsky, H. J., & Brown, R. E. (2006) · BMC Bioinformatics · doi:10.1186/1471-2105-7-123 · Cited by 1,616 · see citing works
Natural neural projection dynamics underlying social behavior
Gunaydin, L. A., Grosenick, L., Finkelstein, J. C., Kauvar, I. V., Fenno, L. E., Adhikari, A., Lammel, S., Mirzabekov, J. J., Airan, R. D., Zalocusky, K. A., et al. (2014) · Cell · doi:10.1016/j.cell.2014.05.017 · Cited by 1,389 · see citing works
The effects of social deprivation on adolescent development and mental health
Orben, A., Tomova, L., & Blakemore, S.-J. (2020) · The Lancet Child & Adolescent Health · doi:10.1016/s2352-4642(20)30186-3 · Cited by 1,229 · cited 2× · see citing works
“The adverse effects of social isolation are particularly apparent for adolescents (Almeida et al., 2021; Orben et al., 2020).”
BackgroundDrugs of Abuse and Stress Trigger a Common Synaptic Adaptation in Dopamine Neurons
Saal, D., Dong, Y., Bonci, A., & Malenka, R. C. (2003) · Neuron · doi:10.1016/s0896-6273(03)00021-7 · Cited by 1,147 · see citing works
A critical period for social experience-dependent oligodendrocyte maturation and myelination
Makinodan, M., Rosen, K. M., Ito, S., & Corfas, G. (2012) · Science · doi:10.1126/science.1220845 · Cited by 922 · see citing works
Adolescence as a neurobiological critical period for the development of higher-order cognition
Larsen, B., & Luna, B. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.09.005 · Cited by 853 · see citing works
Formation of accumbens GluR2-lacking AMPA receptors mediates incubation of cocaine craving
Conrad, K. L., Tseng, K. Y., Uejima, J. L., Reimers, J. M., Heng, L.-J., Shaham, Y., Marinelli, M., & Wolf, M. E. (2008) · Nature · doi:10.1038/nature06995 · Cited by 790 · see citing works
Toward a neurology of loneliness
Cacioppo, S., Capitanio, J. P., & Cacioppo, J. T. (2014) · Psychological Bulletin · doi:10.1037/a0037618 · Cited by 623 · see citing works
Gating of social reward by oxytocin in the ventral tegmental area
Hung, L. W., Neuner, S., Polepalli, J. S., Beier, K. T., Wright, M., Walsh, J. J., Lewis, E. M., Luo, L., Deisseroth, K., Dölen, G., et al. (2017) · Science · doi:10.1126/science.aan4994 · Cited by 578 · see citing works
The neurobiology of social play behavior in rats
Vanderschuren, L. J. M. J., Niesink, R. J. M., & Van Pee, J. M. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00020-6 · Cited by 559 · see citing works
Psychological Consequences of Social Isolation During COVID-19 Outbreak
Pietrabissa, G., & Simpson, S. (2020) · Frontiers in Psychology · doi:10.3389/fpsyg.2020.02201 · Cited by 431 · see citing works
Bellone, C., & Lüscher, C. (2006) · Nature Neuroscience · doi:10.1038/nn1682 · Cited by 429 · see citing works
Self-citationDorsal raphe dopamine neurons represent the experience of social isolation
Matthews, G. A., Nieh, E. H., Vander Weele, C. M., Halbert, S. A., Pradhan, R. V., Yosafat, A. S., Glober, G. F., Izadmehr, E. M., Thomas, R. E., Lacy, G. D., et al. (2016) · Cell · doi:10.1016/j.cell.2015.12.040 · Cited by 402 · see citing works
Forced Social Isolation and Mental Health: A Study on 1,006 Italians Under COVID-19 Lockdown
Pancani, L., Marinucci, M., Aureli, N., & Riva, P. (2021) · Frontiers in Psychology · doi:10.3389/fpsyg.2021.663799 · Cited by 382 · see citing works
Oxytocin enhances social recognition by modulating cortical control of early olfactory processing
Oettl, L.-L., Ravi, N., Schneider, M., Scheller, M. F., Schneider, P., Mitre, M., da Silva Gouveia, M., Froemke, R. C., Chao, M. V., Young, W. S., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.03.033 · Cited by 359 · see citing works
Biased Oxytocinergic Modulation of Midbrain Dopamine Systems
Xiao, L., Priest, M. F., Nasenbeny, J., Lu, T., & Kozorovitskiy, Y. (2017) · Neuron · doi:10.1016/j.neuron.2017.06.003 · Cited by 292 · see citing works
Acute social isolation evokes midbrain craving responses similar to hunger
Tomova, L., Wang, K. L., Thompson, T., Matthews, G. A., Takahashi, A., Tye, K. M., & Saxe, R. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-00742-z · Cited by 283 · see citing works
Isolation rearing in rats: pre- and postsynaptic changes in striatal dopaminergic systems
Hall, F. S., Wilkinson, L. S., Humby, T., Inglis, W., Kendall, D. A., Marsden, C. A., & Robbins, T. W. (1998) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(97)00510-8 · Cited by 261 · see citing works
The human oxytocin gene promoter is regulated by estrogens
Richard, S., & Zingg, H. H. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39297-x · Cited by 242 · see citing works
Social isolation and its impact on child and adolescent development: a systematic review
Almeida, I. L. D. L., Rego, J. F., Teixeira, A. C. G., & Moreira, M. R. (2022) · Revista Paulista de Pediatria · doi:10.1590/1984-0462/2022/40/2020385 · Cited by 223 · see citing works
An Allostatic Theory of Oxytocin
Quintana, D. S., & Guastella, A. J. (2020) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2020.03.008 · Cited by 212 · see citing works
Baarendse, P. J. J., Counotte, D. S., O'Donnell, P., & Vanderschuren, L. J. M. J. (2013) · Neuropsychopharmacology · doi:10.1038/npp.2013.47 · Cited by 206 · see citing works
Solié, C., Girard, B., Righetti, B., Tapparel, M., & Bellone, C. (2022) · Nature Neuroscience · doi:10.1038/s41593-021-00972-9 · Cited by 186 · see citing works
Self-citationThe role of social isolation in social anxiety disorder: a systematic review and meta-analysis
Teo, A. R., Lerrigo, R., & Rogers, M. A. M. (2013) · Journal of Anxiety Disorders · doi:10.1016/j.janxdis.2013.03.010 · Cited by 184 · see citing works
Mameli, M., Bellone, C., Brown, M. T. C., & Lüscher, C. (2011) · Nature Neuroscience · doi:10.1038/nn.2763 · Cited by 177 · see citing works
Self-citationSocial deprivation enhances VTA synaptic plasticity and drug-induced contextual learning
Whitaker, L. R., Degoulet, M., & Morikawa, H. (2013) · Neuron · doi:10.1016/j.neuron.2012.11.022 · Cited by 177 · see citing works
Short-term isolation increases social interactions of male rats: A parametric analysis
Niesink, R. J. M., & van Ree, J. M. (1982) · Physiology & Behavior · doi:10.1016/0031-9384(82)90331-6 · Cited by 175 · see citing works
Bariselli, S., Hörnberg, H., Prévost-Solié, C., Musardo, S., Hatstatt-Burklé, L., Scheiffele, P., & Bellone, C. (2018) · Nature Communications · doi:10.1038/s41467-018-05382-3 · Cited by 171 · see citing works
Self-citationYamamuro, K., Bicks, L. K., Leventhal, M. B., Kato, D., Im, S., Flanigan, M. E., Garkun, Y., Norman, K. J., Caro, K., Sadahiro, M., et al. (2020) · Nature Neuroscience · doi:10.1038/s41593-020-0695-6 · Cited by 169 · see citing works
SHANK3 controls maturation of social reward circuits in the VTA
Bariselli, S., Tzanoulinou, S., Glangetas, C., Prévost-Solié, C., Pucci, L., Viguié, J., Bezzi, P., O'Connor, E. C., Georges, F., Lüscher, C., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4319 · Cited by 168 · see citing works
Self-citationBredewold, R., Smith, C. J. W., Dumais, K. M., & Veenema, A. H. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00216 · Cited by 157 · see citing works
Rescue of oxytocin response and social behaviour in a mouse model of autism
Hörnberg, H., Pérez-Garci, E., Schreiner, D., Hatstatt-Burklé, L., Magara, F., Baudouin, S., Matter, A., Nacro, K., Pecho-Vrieseling, E., & Scheiffele, P. (2020) · Nature · doi:10.1038/s41586-020-2563-7 · Cited by 154 · see citing works
Critical age windows for neurodevelopmental psychiatric disorders: evidence from animal models
Marco, E. M., Macrì, S., & Laviola, G. (2011) · Neurotoxicity Research · doi:10.1007/s12640-010-9205-z · Cited by 144 · see citing works
GluA2-lacking, calcium-permeable AMPA receptors--inducers of plasticity?
Man, H.-Y. (2011) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.01.001 · Cited by 142 · see citing works
Resendez, S. L., Namboodiri, V. M. K., Otis, J. M., Eckman, L. E. H., Rodriguez-Romaguera, J., Ung, R. L., Basiri, M. L., Kosyk, O., Rossi, M. A., Dichter, G. S., et al. (2020) · The Journal of Neuroscience · doi:10.1523/jneurosci.1515-18.2020 · Cited by 142 · see citing works
Hammock, E. A. D. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00195 · Cited by 115 · see citing works
Mechanisms of Channel Block in Calcium-Permeable AMPA Receptors
Twomey, E. C., Yelshanskaya, M. V., Vassilevski, A. A., & Sobolevsky, A. I. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.027 · Cited by 106 · see citing works
Goel, A., Xu, L. W., Snyder, K. P., Song, L., Goenaga-Vazquez, Y., Megill, A., Takamiya, K., Huganir, R. L., & Lee, H.-K. (2011) · PLoS ONE · doi:10.1371/journal.pone.0018264 · Cited by 103 · see citing works
Yamamuro, K., Yoshino, H., Ogawa, Y., Makinodan, M., Toritsuka, M., Yamashita, M., Corfas, G., & Kishimoto, T. (2018) · Cerebral Cortex · doi:10.1093/cercor/bhx010 · Cited by 86 · see citing works
Oxytocin during Development: Possible Organizational Effects on Behavior
Miller, T. V., & Caldwell, H. K. (2015) · Frontiers in Endocrinology · doi:10.3389/fendo.2015.00076 · Cited by 79 · see citing works
Rivera-Irizarry, J. K., Skelly, M. J., & Pleil, K. E. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00129 · Cited by 72 · see citing works
Tang, Y., Chen, Z., Tao, H., Li, C., Zhang, X., Tang, A., & Liu, Y. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.10.004 · Cited by 68 · see citing works
Takatsu-Coleman, A. L., Patti, C. L., Zanin, K. A., Zager, A., Carvalho, R. C., Borçoi, A. R., Ceccon, L. M. B., Berro, L. F., Tufik, S., Andersen, M. L., et al. (2013) · Journal of Psychiatry and Neuroscience · doi:10.1503/jpn.120050 · Cited by 66 · see citing works
Estrogenic regulation of social behavior and sexually dimorphic brain formation
Ogawa, S., Tsukahara, S., Choleris, E., & Vasudevan, N. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.10.012 · Cited by 60 · see citing works
Sex Differences in the Embryonic Development of the Central Oxytocin System in Mice
Tamborski, S., Mintz, E. M., & Caldwell, H. K. (2016) · Journal of Neuroendocrinology · doi:10.1111/jne.12364 · Cited by 55 · see citing works
Ventral tegmental area subcircuits process rewarding and aversive experiences
Bariselli, S., Glangetas, C., Tzanoulinou, S., & Bellone, C. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13779 · Cited by 51 · see citing works
Self-citationKuniishi, H., Yamada, D., Wada, K., Yamada, M., & Sekiguchi, M. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0837-3 · Cited by 47 · see citing works
Yi, E.-S., Oh, S., Lee, J.-K., & Leem, Y.-H. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.03.093 · Cited by 45 · see citing works
Association of youth age at exposure to household dysfunction with outcomes in early adulthood.
Andersen, S. H. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.32769 · Cited by 45 · see citing works
Critical Periods in Child Development and the Transition to Adulthood
Graf, G. H.-J., Biroli, P., & Belsky, D. W. (2021) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.33359 · Cited by 39 · see citing works
Effects of neonatal oxytocin manipulation on development of social behaviors in mice
Mogi, K., Ooyama, R., Nagasawa, M., & Kikusui, T. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.05.010 · Cited by 37 · see citing works
Garcia-Bereguiain, M. A., Gonzalez-Islas, C., Lindsly, C., Butler, E., Hill, A. W., & Wenner, P. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.4025-12.2013 · Cited by 26 · see citing works
Lampert, C., Arcego, D. M., de Sá Couto‐Pereira, N., dos Santos Vieira, A., Toniazzo, A. P., Krolow, R., Garcia, E., Vendite, D. A., Calcagnotto, M. E., & Dalmaz, C. (2017) · International Journal of Developmental Neuroscience · doi:10.1016/j.ijdevneu.2017.05.003 · Cited by 24 · see citing works
Templer, V. L., Wise, T. B., Dayaw, K. I. T., & Dayaw, J. N. T. (2018) · Journal of comparative psychology · doi:10.1037/com0000112 · Cited by 24 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Social isolation and the brain: effects and mechanisms
Xiong, Y., Hong, H., Liu, C., & Zhang, Y. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01835-w · Cited by 127 · see citing works
Neurobiology of Loneliness, Isolation, and Loss: Integrating Human and Animal Perspectives
Vitale, E. M., & Smith, A. S. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.846315 · Cited by 112 · see citing works
Detection, processing and reinforcement of social cues: regulation by the oxytocin system
Menon, R., & Neumann, I. D. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00759-w · Cited by 100 · see citing works
A hypothalamic circuit underlying the dynamic control of social homeostasis
Liu, D., Rahman, M., Johnson, A., Amo, R., Tsutsui‐Kimura, I., Sullivan, Z. A., Pena, N., Talay, M., Logeman, B. L., Finkbeiner, S., et al. (2025) · Nature · doi:10.1038/s41586-025-08617-8 · Cited by 83 · see citing works
Neural circuits regulating prosocial behaviors
Walsh, J. J., Christoffel, D. J., & Malenka, R. C. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01348-8 · Cited by 72 · see citing works
The Formation and Function of the VTA Dopamine System
Hou, G., Hao, M., Duan, J., & Han, M.-H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25073875 · Cited by 65 · see citing works
Dynamic influences on the neural encoding of social valence
Padilla-Coreano, N., Tye, K. M., & Zelikowsky, M. (2022) · Nature reviews. Neuroscience · doi:10.1038/s41583-022-00609-1 · Cited by 57 · see citing works
The modulation of emotional and social behaviors by oxytocin signaling in limbic network
Triana-Del Rio, R., Ranade, S., Guardado, J., LeDoux, J., Klann, E., & Shrestha, P. (2022) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2022.1002846 · Cited by 58 · see citing works
Interaction of acetylcholine and oxytocin neuromodulation in the hippocampus
Zhang, Y., Karadas, M., Liu, J., Gu, X., Vöröslakos, M., Li, Y., Tsien, R. W., & Buzsáki, G. (2024) · Neuron · doi:10.1016/j.neuron.2024.02.021 · Cited by 56 · see citing works
Rappeneau, V., & Castillo Díaz, F. (2024) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2024.105675 · Cited by 51 · see citing works
Brain circuits that regulate social behavior
Li, H., Zhao, Z., Jiang, S., & Wu, H. (2025) · Molecular Psychiatry · doi:10.1038/s41380-025-03037-6 · Cited by 57 · see citing works
Bordes, J., Miranda, L., Müller‐Myhsok, B., & Schmidt, M. V. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105243 · Cited by 42 · see citing works
Endogenous oxytocin exerts anti-nociceptive and anti-inflammatory effects in rats
Nishimura, H., Yoshimura, M., Shimizu, M., Sanada, K., Sonoda, S., Nishimura, K., Baba, K., Ikeda, N., Motojima, Y., Maruyama, T., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03879-8 · Cited by 34 · see citing works
Affectionate touch and diurnal oxytocin levels: An ecological momentary assessment study
Schneider, E., Hopf, D., Aguilar‐Raab, C., Scheele, D., Neubauer, A., Sailer, U., Hurlemann, R., Eckstein, M., & Ditzen, B. (2023) · eLife · doi:10.7554/elife.81241 · Cited by 46 · see citing works
Social isolation shortens lifespan through oxidative stress in ants
Koto, A., Tamura, M., Wong, P. S., Aburatani, S., Privman, E., Stoffel, C., Crespi, A., McKenzie, S. K., Mendola, C. L., Kay, T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-41140-w · Cited by 29 · see citing works
Interconnected neural circuits mediating social reward
Isaac, J., & Murugan, M. (2024) · Trends in Neurosciences · doi:10.1016/j.tins.2024.10.004 · Cited by 25 · see citing works
Broadfoot, C. K., Lenell, C., Kelm‐Nelson, C. A., & Ciucci, M. R. (2022) · SSRN Electronic Journal · doi:10.1016/j.bbr.2022.114157 · Cited by 15 · see citing works
Complexity of the Hypothalamic Oxytocin System and its Involvement in Brain Functions and Diseases
Cui, X., & Xiao, L. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01424-1 · Cited by 16 · see citing works
Polycystic Ovary Syndrome Pathophysiology: Integrating Systemic, CNS and Circadian Processes
Anderson, G. (2024) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2901024 · Cited by 14 · see citing works
Chang, H.-T., Cheng, K., Hung, Y.-C., & Hsu, K. (2025) · Journal of Biomedical Science · doi:10.1186/s12929-025-01130-0 · Cited by 14 · see citing works
Loisy, M., Farah, A. T., Fafouri, A., Fanton, A., Ahmadi, M., Therreau, L., Chevaleyre, V., & Piskorowski, R. A. (2022) · Hippocampus · doi:10.1002/hipo.23478 · Cited by 13 · see citing works
Dopamine dynamics underlying maternal motivation and reward
Day, K. R., & Shea, S. D. (2025) · Neuroscience Research · doi:10.1016/j.neures.2025.104928 · Cited by 13 · see citing works
Zhao, X., Chae, Y. C., Smith, D., Chen, V., DeFelipe, D., Sokol, J. W., Sadangi, A., & Tschida, K. (2024) · eLife · doi:10.7554/elife.94924.3 · Cited by 13 · see citing works
Oxytocin signaling regulates maternally directed behavior during early life
Zelmanoff, D. D., Bornstein, R., Kaufman, M., Dine, J., Wietek, J., Litvin, A., Abraham, S., Cohen, S., Atzmon, A., Porat, I., et al. (2025) · Science · doi:10.1126/science.ado5609 · Cited by 12 · see citing works
Raymond, J. S., Rehn, S., James, M. H., Everett, N. A., & Bowen, M. T. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00612-4 · Cited by 12 · see citing works
Gora, C., Dudas, A., Court, L., Annamneedi, A., Lefort, G., Nakahara, T. S., Azzopardi, N., Acquistapace, A., Lainé, A.-L., Trouillet, A., et al. (2024) · Translational Psychiatry · doi:10.1038/s41398-024-03174-6 · Cited by 12 · see citing works
Conserved multisensory integration of social cues in the thalamus
Anneser, L., & Kappel, J. M. (2024) · iScience · doi:10.1016/j.isci.2024.111678 · Cited by 9 · see citing works
Roles of AMPA receptors in social behaviors
Xu, Q. W., Larosa, A., & Wong, T. P. (2024) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2024.1405510 · Cited by 6 · see citing works
Chen, X., Kim, Y., & Kawaguchi, D. (2025) · Frontiers in Neural Circuits · doi:10.3389/fncir.2025.1568610 · Cited by 9 · see citing works
Stanisavljević, A., & Filipović, D. (2024) · Pharmaceuticals · doi:10.3390/ph17111527 · Cited by 7 · see citing works
Oxytocin and dopamine in psychostimulant-induced changes in social behaviour
Díaz, F. C., Neumann, I. D., & Rappeneau, V. (2025) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2025.101200 · Cited by 7 · see citing works
Mavrych, V., Mansour, G. K., Hajjar, A. W., & Bolgova, O. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010084 · Cited by 7 · see citing works
Neural control of sex differences in affiliative and prosocial behaviors
Mikulovic, S., & Lenschow, C. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106039 · Cited by 5 · see citing works
Sun, Y., Qian, W., Zhang, L., Niu, H., Li, L., Li, L., Zhu, Y., Xiao, J., Liu, J., Han, X., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09208-z · Cited by 5 · see citing works
Johnston, M. P., & Wanat, M. J. (2022) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2022.1038236 · Cited by 6 · see citing works
Impact of early social isolation on social circuits and behavior: relevance to schizophrenia
Kawatake-Kuno, A., Leventhal, M. B., & Morishita, H. (2025) · Neuropsychopharmacology · doi:10.1038/s41386-025-02156-6 · Cited by 7 · see citing works
Arakawa, H., Tokashiki, M., Higuchi, Y., & Konno, T. (2024) · Peptides · doi:10.1016/j.peptides.2024.171178 · Cited by 4 · see citing works
Excess Neonatal Testosterone Causes Male-Specific Social and Fear Memory Deficits in Wild-Type Mice
Quiñones-Labernik, P., Blocklinger, K. L., Bruce, M. R., Hagan, E., Preuschl, D., Tesar, C., & Ferri, S. L. (2025) · eneuro · doi:10.1523/eneuro.0020-25.2025 · Cited by 4 · see citing works
“The ventral tegmental area, nucleus accumbens, and cerebellum have also been implicated in the regulation of social behavior (Gunaydin et al., 2014; Carta et al., 2019; Porcelli et al., 2019; Musardo et al., 2022; Solié et al., 2022).”
Enhanced social motivation in briefly isolated male rats
Toyoshima, M., & Yamada, K. (2023) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2023.08.2195 · Cited by 4 · see citing works
Wnuk, H. K., Orden, K. A. V., & Wang, K. H. (2025) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2025.106451 · Cited by 4 · see citing works
Tabaka, O., Lawal, S. A., Triana, R. D. R., Hou, M., Fraser, A., Gallagher, A., Ruiz, K. S. A., Marmarcz, M., Dickinson, M., Oliveira, M. M., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-09193-3 · Cited by 3 · see citing works
Zhou, J., Yin, Z., Chen, Z., Fu, H., Li, Q., Li, S., Zhang, Y., Zhang, X., Tang, D., Li, A., et al. (2025) · Advanced Science · doi:10.1002/advs.202406192 · Cited by 4 · see citing works
Oxytocin impairs wound-healing during social isolation but not social living
Hammond, E., Monari, P. K., Kilponen, L., Chen, Y., Auger, A. P., & Marler, C. A. (2025) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2025.107445 · Cited by 3 · see citing works
Wu, W. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.107645 · Cited by 3 · see citing works
Geng, S., Zhang, Z., Liu, X., Sun, H., Xu, T., Sun, C., Hu, S., Liu, A., Yang, Z., Xie, W., et al. (2024) · Physiology & Behavior · doi:10.1016/j.physbeh.2024.114788 · Cited by 3 · see citing works
Zhao, Z., Wang, Y.-C., Chen, P., Tzeng, S., Chen, P.-S., & Kuo, Y. (2025) · Behavioral and Brain Functions · doi:10.1186/s12993-025-00269-y · Cited by 3 · see citing works
Sukhchuluun, G., Wang, Z., Wang, D., & Zhang, X.-Y. (2025) · Neuroscience · doi:10.1016/j.neuroscience.2025.04.020 · Cited by 2 · see citing works
Zheng, Q., Zhao, Y., Cheng, Q., Wang, H., Liu, F., Lai, J., Liu, Y., Zhang, X., Kang, Y., Li, Z., et al. (2025) · Journal of Neuroscience · doi:10.1523/jneurosci.0382-25.2025 · Cited by 2 · see citing works
Tan, H., Jin, S., Lv, W., Guo, L., Jiang, P., Li, Y., Shi, M., Wang, D., Wang, Y., & Bao, A. (2025) · Neuroscience Bulletin · doi:10.1007/s12264-025-01475-4 · Cited by 2 · see citing works
Dudas, A., Novak, A., Gora, C., Pecnard, E., Azzopardi, N., Morisset‐Lopez, S., & Pellissier, L. P. (2025) · Scientific Reports · doi:10.1038/s41598-025-26215-6 · Cited by 2 · see citing works
Qi, Y., Weng, S., Yin, Q., Li, M., Shen, L., Qiao, E., Gao, L., Wang, Y., Li, Y., Luo, W., et al. (2026) · Interdisciplinary medicine · doi:10.1002/inmd.70118 · Cited by 2 · see citing works
Silkis, I. G. (2024) · Neurochemical Journal · doi:10.1134/s1819712424010215 · Cited by 2 · see citing works
Zhao, X., Chae, Y. C., Smith, D., Chen, V., DeFelipe, D., Sokol, J. W., Sadangi, A., & Tschida, K. (2024) · eLife · doi:10.7554/elife.94924.1 · Cited by 2 · see citing works
Oxytocin as a modulator of adaptive behavior: integrating ingestive and social mechanisms
Moseley, P. E., Hammock, E. A. D., & Williams, D. L. (2025) · Physiology & Behavior · doi:10.1016/j.physbeh.2025.114992 · Cited by 1 · see citing works
Reunion with a peer partner reduces PVN oxytocin neuron immunoreactivity in socially selective voles
Goodwin, N. L., Licata, A. M., Power, K. C., Reitz, K. M., Kamal, Y., & Beery, A. K. (2025) · Scientific Reports · doi:10.1038/s41598-025-17920-3 · Cited by 1 · see citing works
Neural Circuits of Social and Physiological Needs
Liu, D., & Dulac, C. G. (2025) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-112723-025633 · Cited by 1 · see citing works
Factors Modulating the Effects of Juvenile Social Isolation on Adult Social Behavior in Rodents
Leventhal, M. B., Kawatake-Kuno, A., Lidoski, A., & Morishita, H. (2026) · Developmental Psychobiology · doi:10.1002/dev.70129 · Cited by 1 · see citing works
A narrative review on oxytocin at the intersection of sleep, stress, and social behavior
Boccalaro, I. L., Rillosi, E., Ramírez‐Plascencia, O. D., Luca, R. D., & Mahoney, C. E. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1745281 · Cited by 2 · see citing works
Regulation of Oxytocin on Empathy and Its Neural Mechanism
Yue, G. (2023) · IntechOpen eBooks · doi:10.5772/intechopen.112743 · Cited by 1 · see citing works
Susceptibility of Glucose Regulation to Social IsolationPreprint
Lamont, H., Ooyama, R., Muñoz, P. D., Siegel, D. M., Baringanire, P., Vargas, V., Bocarsly, M. E., Routh, V. H., & Carcea, I. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.18.695168 · Cited by 1 · see citing works
Interaction of nicotine and social reward in group-reared male adolescent rats
Cortés‐Patiño, D. M., Neira, V. M., Ballesteros-Acosta, H., Bustos-Rangel, A., & Lamprea, M. R. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114432
Liu, J., Bai, Y., Fu, R., Lin, M., Li, J., Nie, L., Dang, X., Wang, Q., Zhu, Y., Lu, L., et al. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4852483
Aberrant TSC-Rheb axis in Oxytocin receptor+ cells mediate stress-induced anxietyPreprint
Tabaka, O., Lawal, S., Triana, R. D. R., Hou, M., Fraser, A., Gallagher, A., Ruiz, K. S. A., Marmarcz, M., Dickinson, M., Oliveira, M. M., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.25.600464
Qasim, H. O., Jaber, I. M., Ahmed, S. M., & Merkhan, M. M. (2024) · Review of Clinical Pharmacology and Pharmacokinetics - International Edition · doi:10.61873/tozb6842
Neurobiological mechanisms of social recognition memory
Park, G., & Lee, Y. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-15754-7.00027-4
Zhao, X., Chae, Y. C., Smith, D., Chen, V., DeFelipe, D., Sokol, J. W., Sadangi, A., & Tschida, K. (2025) · eLife · doi:10.7554/elife.94924.2
Liu, J., Zhang, W., Bai, Y., Fu, R., Lin, M., Li, J., Nie, L., Dang, X., Wang, Q., Zhu, Y., et al. (2025) · Neuroendocrinology · doi:10.1159/000544839
Dopamine D2 receptors in the cerebellum: modulation of social behavior
Ox, D. A., Shuvaev, А. N., Shuvaev, А. N., & Semyonova, A. A. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152238 · Cited by 2 · see citing works
Ocytocine versus dopamine : l’équilibre délicat entre lien social et addiction
Rappeneau, V., & Díaz, F. C. (2025) · Biologie Aujourd hui · doi:10.1051/jbio/2025012
Zheng, Q., Tian, Y., Wu, Y., Wang, H., Zhang, Y., Zhang, Y., Wang, Y., Zhao, Y., Di, Y., Fan, J., et al. (2026) · Behavioural Brain Research · doi:10.1016/j.bbr.2026.116178
Zheng, S., Prounis, G. S., & Ophir, A. G. (2026) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2026.1772423
Circuit logic of oxytocin and vasopressin complementary actions
Jeanneteau, F. D., Chakraborty, P., Petitjean, H., & Charlet, A. (2026) · Frontiers in Neuroscience · doi:10.3389/fnins.2026.1875731
Bensing, P. C., Bowers, C. P., Moosa, I., & Leong, K.-C. (2026) · Neuroscience Letters · doi:10.1016/j.neulet.2026.138731
Loveren, E. V., Alfos, S., Guu, S. F., Ducroix‐Crepy, C., Hernández‐Ramírez, S., Ferreira, G., & Lafenetre, P. (2026) · Journal of Neuroendocrinology · doi:10.1111/jne.70300
- Authors
- Musardo, S., Contestabile, A., Knoop, M., Baud, O., & Bellone, C.
- Affiliations
- University of Geneva (CH)
- Laboratory of Child Growth and Development, University of Geneva
- Corresponding author
- Bellone, Camilla
- Venue
- eLife
- Publisher
- eLife Sciences Publications, Ltd
- Published
- 2022-04-22
- Volume
- 11
- ISSN
- 2050-084X (ISSN-L)
- PMC
- PMC9075949
- OpenAlex
- W4224239502
- Semantic Scholar
- 35a5a42e0142fb2a032f926250e41d0089801b2c
- Cited by
- 77
- References
- 56
- Citations by year
- 2026: 8 · 2025: 31 · 2024: 20 · 2023: 9 · 2022: 9
- FWCI
- 16.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- eLife (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by-nc)
- Funders
- Swiss National Science Foundation (31003A_182326)
- European Research Council (Consolidator grant 864552)
- NCCR Synapsy (51NF40-185897)
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- social isolation, oxytocin neurons, paraventricular nucleus, ventral tegmental area, dopaminergic neurons, social interaction, social novelty preference, reward systems, prefrontal cortex, chemogenetic inhibition, synaptic plasticity, homeostatic adaptation, social skills development
- MeSH terms
- Animals, Male, Neurons, Oxytocin, Reward, Social Isolation, Ventral Tegmental Area, Mice, Dopaminergic Neurons
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 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
