Effects of Maternal Deprivation and Complex Housing on Rat Social Behavior in Adolescence and Adulthood

Up to 24 h, longer periods of isolation induce more play in rats.

“Indeed, up to 24 h, longer periods of isolation induce more play (Panksepp and Beatty, 1980), but see Manduca et al. (2016) for an exception.”

• cites Panksepp and Beatty, 1980 sourceNot checked — no full text of the source
• cites Manduca et al., 2016 sourceDisputed

  Manduca et al. is cited as an exception to the claim that longer isolation increases play up to 24 hours. Instead, the paper’s section on pharmacological manipulation of nucleus accumbens dopamine reports that vehicle-treated rats isolated for 24 hours showed about twice as much social play as rats isolated for 2 hours. Our copy provides no page number for this passage. (LLM, conf=0.87)

  Checked by a reasoning model — may be wrong.

  Experimental — accuracy not yet measured

3 h of daily maternal separation reduced social interest in both adult male and female mandarin voles and mice.

“It was observed that 3 h of daily maternal separation reduced social interest (i.e., time spent exploring a conspecific) in both adult male and female mandarin voles (Wei et al., 2013; Yu et al., 2013) and mice (Tsuda and Ogawa, 2012; Zoicas and Neumann, 2016).”

• cites Wei et al., 2013 sourceNot checked — no full text of the source
• cites Yu et al., 2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Tsuda and Ogawa, 2012 sourcePartly supported

  The Methods (Maternal Separation Procedure) report daily 3-hour separation and specify that only female offspring mice were studied. The Results (MS Effects on Social Preference Patterns) report less social investigation by separated adult females. This source does not establish the claim for adult male mice; the vole findings are attributed to other citations in the sentence. (LLM, conf=0.88)

  Experimental — accuracy not yet measured

Early life context and stressful experiences increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain.

“Early life context and stressful experiences are known to increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain.”

• Also stated in: § Introduction · boosted

  “An adverse early life environment is known to increase the risk of developing psychiatric disorders later in life, including disorders with deficits in the social domain (Dube et al., 2003; Carr et al., 2013).”

• cites Dube et al., 2003 sourcePartly supported

  The Abstract reports that adverse childhood experiences were associated with higher risks of depressed affect, suicide attempts, and alcoholism in adulthood. It does not report diagnoses of psychiatric disorders with deficits in the social domain, so that extension of the claim is unsupported. (LLM, conf=0.86)

  Experimental — accuracy not yet measured
• cites Carr et al., 2013 sourceNot checked — no full text of the source

The amount of maternal care received in the first week of life positively correlates with the amount of social play behavior in adolescent male but not female rats.

“Recently, our lab showed a positive correlation between the amount of maternal care received in the first week of life and the amount of social play behavior in adolescent male but not female rats (Van Hasselt et al., 2012)”

• cites Van Hasselt et al., 2012 sourceSupported

Adolescence is a sensitive period in which environmental influences can impact brain development.

“Besides the early postnatal period, adolescence is gaining interest as a sensitive period in which environmental influences can impact brain development (Fuhrmann et al., 2015).”

• cites Fuhrmann et al., 2015 sourceSupported

Maternally deprived animals showed a lower body weight in adolescence.

“Consistent with previous studies (Marco et al., 2015; van der Veen et al., 2015; Kentrop et al., 2016), maternally deprived animals showed a lower body weight in adolescence.”

• cites Marco et al., 2015 sourceNot checked — no full text of the source
• cites van der Veen et al., 2015 sourceSupported
• cites Kentrop et al., 2016 sourceSupported

Complex housed rats habituate faster to novel situations.

“Previously we and others have shown that complex housed rats habituate faster to novel situations (Zimmermann et al., 2001; Moncek et al., 2004; van der Veen et al., 2015)”

• cites Zimmermann et al., 2001 sourceNot checked — no full text of the source
• cites Moncek et al., 2004 sourceNot checked — no full text of the source
• cites van der Veen et al., 2015 sourceSupported

Males are more affected than females in a broad range of behavioral domains following early postnatal manipulations of maternal care in rodents.

“Focusing on early postnatal manipulations of maternal care in rodents as a model for ELS, it seems that males are more affected than females in a broad range of behavioral domains (Loi et al., 2017; Schroeder et al., 2018).”

• cites Loi et al., 2017 sourceSupported
• cites Schroeder et al., 2018 sourcePartly supported

  The Conclusions (section 6; page not provided) say that males seem more susceptible to early-life stress than females, but qualify this as based on only a few sex-specific studies. Section 2 reports greater effects in males for behavioral despair and alcohol preference after postnatal stress; it does not establish greater effects in males across a broad range of behavioral domains, and also describes a combined-stress model in which females showed anhedonia. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

Males receive more maternal care from their mothers compared to females.

“One potential explanation is that males, compared to females, receive more maternal care from their mothers (Moore and Morelli, 1979; Van Hasselt et al., 2012).”

• cites Moore and Morelli, 1979 sourceNot checked — no full text of the source
• cites Van Hasselt et al., 2012 sourceSupported

Complex housed animals appear to quickly integrate a novel environment.

“In general, complex housed animals appear to quickly integrate a novel environment (van der Veen et al., 2015)”

• cites van der Veen et al., 2015 sourceSupported

Complex housed male rats showed less social interest in adulthood.

“Only complex housed males truly showed more social play behavior here, while showing less social interest in adulthood.”

• Also stated in: § Adult Three-Chamber Social Approach Task · plain

  “In the social interest phase, complex housed rats spent less time with the unfamiliar rat [Housing F(1,60) = 8.01, p < 0.01, ηp2 = 0.12, Supplementary Table S3] and showed a reduced preference for the cylinder zone containing an unfamiliar rat compared to standard housed males [F(1,60) = 4.79, p < 0.05, ηp2 = 0.07]”

• AssumptionRests on an assumption: Rats prefer exploring conspecifics over inanimate objects.

Complex housing did not moderate the effects of maternal deprivation.

“Complex housing did not moderate the effects of MD, but in itself induced a strong behavioral phenotype.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “Complex housing did not moderate the effects of MD (Supplementary Table S2).”

Only complex housed male rats truly showed more social play behavior after 24 h isolation.

“Only complex housed males truly showed more social play behavior here, while showing less social interest in adulthood.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “Contrary to the reduction in social play seen after 3 h of isolation, complex housed males showed a significantly higher amount of social play behavior compared to standard housed males after 24 h of isolation [F(1,36) = 9.44, p < 0.01, ηp2 = 0.21; Figure 2A].”

After 24 h of isolation, complex housed rats showed shorter latencies to engage in social play behavior.

“However, after 24 h of isolation, these animals showed shorter latencies to engage in social play behavior.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “However, like males, complex housed females showed a shorter latency to engage in social play [F(1,47) = 11.96, p < 0.001, ηp2 = 0.20; Figure 3B]”

Both complex housed male and female rats hardly displayed any play behavior after a 3 h isolation period.

“Both complex housed males and females hardly displayed any play behavior after a 3 h isolation period.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “However, both male and female complex housed animals showed minimal amounts of social play behavior compared to standard housed rats [number of pins males: F(1,28) = 23.22, p < 0.001, ηp2 = 0.45, females: F(1,26) = 28.11, p < 0.001, ηp2 = 0.52].”

Maternally deprived male rats showed a longer latency to play after 24 h isolation.

“Maternally deprived males – but not females – showed a longer latency to play and a decreased total amount of social play behavior, after a 24 h isolation period.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “In male animals, MD was associated with a decreased amount of social play [number of pins F(1,36) = 5.49, p < 0.05, ηp2 = 0.13, Figure 2A], increased latency to engage in social play [latency to pin F(1,36) = 5.65, p < 0.05, ηp2 = 0.14, Figure 2B]”

Maternally deprived male rats showed a decreased total amount of social play behavior after 24 h isolation.

“Maternally deprived males – but not females – showed a longer latency to play and a decreased total amount of social play behavior, after a 24 h isolation period.”

• Also stated in: § Adolescent Social Play Behavior · plain

  “In male animals, MD was associated with a decreased amount of social play [number of pins F(1,36) = 5.49, p < 0.05, ηp2 = 0.13, Figure 2A]”

In adulthood, social discrimination was impaired in deprived male and female rats in the three-chamber social approach task.

“In adulthood, social discrimination was impaired in deprived male and female rats in the three-chamber social approach task.”

• AssumptionRests on an assumption: Given the choice between a familiar and unfamiliar rat, rats are expected to explore the unfamiliar stimulus rat.

In male animals after 24 h isolation, maternal deprivation was associated with increased social exploration.

“and increased social exploration [F(1,36) = 5.13, p < 0.05, ηp2 = 0.13, Figure 2D].”

Complex housed males showed an increase in social exploration after 24 h isolation.

“and an increase in social exploration [F(1,36) = 8.64, p < 0.01, ηp2 = 0.19; Figure 2D].”

Complex housed males showed a reduced latency to play after 24 h isolation.

“Moreover, complex housed males showed a reduced latency to play [F(1,36) = 11.77, p < 0.01, ηp2 = 0.25; Figure 2B]”

Maternal deprivation did not interact with the effects of housing in females after 24 h isolation.

“MD did not interact with the effects of housing.”

In male animals after 24 h isolation, maternal deprivation was associated with an increased latency to engage in social play.

“increased latency to engage in social play [latency to pin F(1,36) = 5.65, p < 0.05, ηp2 = 0.14, Figure 2B]”

Both male and female complex housed animals showed minimal amounts of social play behavior compared to standard housed rats after 3 h isolation.

“However, both male and female complex housed animals showed minimal amounts of social play behavior compared to standard housed rats [number of pins males: F(1,28) = 23.22, p < 0.001, ηp2 = 0.45, females: F(1,26) = 28.11, p < 0.001, ηp2 = 0.52].”

Complex housing did not moderate the effects of maternal deprivation in males after 24 h isolation.

“Complex housing did not moderate the effects of MD (Supplementary Table S2).”

Complex housed males showed a significantly higher amount of social play behavior compared to standard housed males after 24 h isolation.

“Contrary to the reduction in social play seen after 3 h of isolation, complex housed males showed a significantly higher amount of social play behavior compared to standard housed males after 24 h of isolation [F(1,36) = 9.44, p < 0.01, ηp2 = 0.21; Figure 2A].”

Independent of early life conditions, complex housing lowered body weight in both males and females.

“Independent of early life conditions, complex housing also lowered body weight in both males and females [as we and others have seen before (Moncek et al., 2004; Peña et al., 2006; Harati et al., 2013; van der Veen et al., 2015)].”

• cites Moncek et al., 2004 sourceNot checked — no full text of the source
• cites Peña et al., 2006Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Harati et al., 2013 sourceNot checked — no full text of the source

In adult male rats, all animals showed a shorter latency to approach the cylinder containing the stimulus rat compared to the empty cylinder.

“All animals showed a shorter latency to approach the cylinder containing the stimulus rat compared to the empty cylinder [location F(1,60) = 25.41, p < 0.001, ηp2 = 0.30; Figure 4B].”

In the social interest phase, complex housed rats spent less time with the unfamiliar rat.

“In the social interest phase, complex housed rats spent less time with the unfamiliar rat [Housing F(1,60) = 8.01, p < 0.01, ηp2 = 0.12, Supplementary Table S3]”

• AssumptionRests on an assumption: Rats prefer exploring conspecifics over inanimate objects.

Complex housed males showed increased pin length after 24 h isolation.

“increased pin length [F(1,36) = 20.67, p < 0.001, ηp2 = 0.37; Figure 2C]”

In adulthood, male complex housed animals showed a decreased social interest at the start of testing.

“In adulthood, male complex housed animals showed a decreased social interest at the start of testing.”

There was no difference in approach latency between the two empty cylinders in any of the groups during habituation.

“Moreover, there were no effects of MD or complex housing on DI during habituation and no difference in approach latency between the two empty cylinders in any of the groups”

The amount of pins and pin length was unaffected by housing condition in females after 24 h isolation.

“In contrast to the males, the amount of pins and pin length was also unaffected by housing condition (Figures 3A,C).”

During the social interest phase, complex housed males showed high levels of initial activity and a more rapid decline in activity over the course of testing compared to standard housed males.

“During the social interest phase, we analyzed the 5-min data over time and indeed saw high levels of initial activity and a more rapid decline in activity over the course of testing in complex compared to standard housed males, but not females [males: time ∗ housing F(1,60) = 11.69, p < 0.005, ηp2 = 0.16, females: time ∗ housing F(1,55) = 0.01, p = 0.91, ηp2 = 0.00, data not shown].”

In adult females, all other female groups preferred the unfamiliar rat over the empty cylinder in both time bins.

“All other female groups preferred the unfamiliar rat over the empty cylinder in both time bins.”

During the habituation phase of the three-chamber task, none of the groups in both male and female experiments had a preference for either of the rooms.

“During the habituation phase, none of the groups in both male and female experiments had a preference for either of the rooms.”

In adult males, the amount of time spent near the rat in the social interest phase did not correlate with the discrimination index of the social discrimination phase.

“However, the amount of time spent near the rat in the social interest phase did not correlate to the DI of the social discrimination phase (Pearson’s r = -0.09, p = 0.47).”

Complex housed females showed increased social exploration compared to standard housed females after 24 h isolation.

“and increased social exploration compared to standard housed females [F(1,47) = 23.14, p < 0.001, ηp2 = 0.33; Figure 3D].”

After 3 h of social isolation, none of the play behaviors were affected by maternal deprivation in males or females.

“After 3 h of social isolation, none of the play behaviors were affected by MD, nor did MD interact with the effects of complex housing in males or females (Table 2).”

Complex housing did not moderate the effects of maternal deprivation in adolescence or adulthood.

“Complex housing did not moderate the effects of MD in adolescence or adulthood.”

Complex housing effects on social interest in adult males were observed in all groups, regardless of maternal deprivation.

“The complex housing effects on social interest were observed in all groups, regardless of MD.”

There were no effects of maternal deprivation or complex housing on discrimination index during habituation.

“Moreover, there were no effects of MD or complex housing on DI during habituation and no difference in approach latency between the two empty cylinders in any of the groups”

In adult females, all other groups showed a preference for the unfamiliar rat in the first time bin.

“All other groups showed a preference for the unfamiliar rat in the first time bin (Supplementary Table S5).”

After 3 h of social isolation, maternal deprivation did not interact with the effects of complex housing on play behaviors in males or females.

“After 3 h of social isolation, none of the play behaviors were affected by MD, nor did MD interact with the effects of complex housing in males or females (Table 2).”

Adolescent complex housed males and females showed very little social play behavior after 3 h of social isolation.

“Adolescent complex housed males and females showed very little social play behavior after 3 h of social isolation”

Complex housing independently affected social behavior.

“Complex housing independently affected social behavior.”

Time spent in social exploration was unaffected by housing condition in both males and females after 3 h isolation.

“Time spent in social exploration was unaffected by housing condition in both males and females (Supplementary Table S1).”

During the social interest phase, complex housed females did not show high levels of initial activity and a more rapid decline in activity over the course of testing compared to standard housed females.

“During the social interest phase, we analyzed the 5-min data over time and indeed saw high levels of initial activity and a more rapid decline in activity over the course of testing in complex compared to standard housed males, but not females [males: time ∗ housing F(1,60) = 11.69, p < 0.005, ηp2 = 0.16, females: time ∗ housing F(1,55) = 0.01, p = 0.91, ηp2 = 0.00, data not shown].”

In male animals after 24 h isolation, maternal deprivation was associated with a decreased amount of social play (number of pins).

“In male animals, MD was associated with a decreased amount of social play [number of pins F(1,36) = 5.49, p < 0.05, ηp2 = 0.13, Figure 2A]”

In adult females, the shorter latency to approach the unfamiliar rat compared to the familiar rat was predominantly seen in maternally deprived standard housed animals.

“This was predominantly seen in the maternally deprived standard housed animals [location ∗ MD ∗ housing F(1,55) = 4.03, p = 0.05, ηp2 = 0.07].”

Complex housed females showed a shorter latency to engage in social play compared to standard housed females after 24 h isolation.

“However, like males, complex housed females showed a shorter latency to engage in social play [F(1,47) = 11.96, p < 0.001, ηp2 = 0.20; Figure 3B]”

In adult females, maternal deprivation influenced the discrimination index over time (time × MD interaction).

“Similar to the male results, MD influenced the DI over time [time ∗ MD F(1,55) = 7.27, p < 0.01, ηp2 = 0.12; Figure 5C]”

In adult females, maternally deprived complex housed females did not show a preference in either time bin.

“The maternally deprived complex housed females did not show a preference in either of the time bins.”

Maternal deprivation did not significantly affect behavior in males in the social interest phase.

“MD did not significantly affect behavior.”

In adult females, there was a significant difference in approach latency between the cylinders, with an overall shorter latency to approach the cylinder containing the unfamiliar rat compared to the familiar rat.

“There was a significant difference in approach latency between the cylinders, with an overall shorter latency to approach the cylinder containing the unfamiliar rat compared to the familiar rat [location F(1,55) = 5.94, p < 0.05, ηp2 = 0.10; Figure 5D].”

In adult females, the amount of time spent near the rat in the social interest phase did not correlate with the discrimination index of the social discrimination phase.

“The amount of time spent near the rat in the social interest phase did not correlate to the DI of the social discrimination phase (Pearson’s r = -0.12, p = 0.36).”

In adult males, maternally deprived animals did not show a preference in either time bin.

“The maternally deprived animals did not show a preference at all in either of the time bins.”

There was no effect of maternal deprivation on any behavioral measures in females after 24 h isolation.

“All females showed social play behavior after 24 h of social isolation, but there was no effect of MD on any of the behavioral measures (Figure 3 and Supplementary Table S2).”

In adult males, maternal deprivation influenced the discrimination index over time (time × MD interaction).

“In the social discrimination phase, MD influenced the DI over time [time ∗ MD F(1,60) = 4.37, p < 0.05, ηp2 = 0.07; Figure 4C]”

Social resting behavior was observed in complex housed animals and was absent in standard housed males and females after 3 h isolation.

“In contrast to social play behavior, we observed social resting behavior in the complex housed animals which was absent in standard housed males [F(1,28) = 16.93, p < 0.001, ηp2 = 0.38] and females [F(1,26) = 8.41, p < 0.01, ηp2 = 0.24].”

The difference in latency to approach the stimulus rat vs empty cylinder was more pronounced in standard housed compared to complex housed male rats.

“This difference was more pronounced in standard compared to complex housed animals [location ∗ housing F(1,60) = 6.31, p < 0.05, ηp2 = 0.10].”

In contrast, social exploration was higher in deprived males.

“In contrast, social exploration was higher in deprived males.”

We found clear effects of maternal deprivation on social discrimination in both sexes.

“We found clear effects of MD on social discrimination in both sexes.”

Both complex housed males and females needed less time to engage in social play after 24 h of isolation.

“Both complex housed males and females needed less time to engage in social play after 24 h of isolation.”

In adulthood, social interest was not affected by maternal deprivation.

“In adulthood, social interest was not affected by MD.”

The effect of complex housing on social play behavior strongly depended on the length of social isolation before the test.

“The effect of complex housing on social play behavior strongly depended on the length of social isolation before the test.”

There were no interaction effects with MD in adult social behavior.

“As with adolescent social play, there were no interaction effects with MD in adult social behavior.”

Both male and female complex housed rats showed increased social exploration of their play partners.

“both male and female complex housed rats also showed increased social exploration of their play partners”

In contrast to non-deprived animals, deprived animals did not discriminate between the unfamiliar and familiar rat.

“In contrast to non-deprived animals, deprived animals did not discriminate between the unfamiliar and familiar rat.”

In both early life settings, males seem to be more influenced by the early life environment compared to females.

“In both early life settings, males seem to be more influenced by the early life environment compared to females.”

Inter-rater reliability for all coded behaviors ranged between 0.97 and 0.99.

“Inter-rater reliability was determined by calculating intraclass correlations for all coded behaviors and ranged between 0.97 and 0.99.”

Early life stress is known to increase aggression in rodents.

“ELS is known to increase aggression in rodents (Veenema et al., 2006, 2007; Zamberletti et al., 2012; Yu et al., 2013; Kohl et al., 2015)”

• cites Veenema et al., 2006, 2007Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Zamberletti et al., 2012 sourceNot checked — no full text of the source
• cites Yu et al., 2013Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

In adult females, all females spent time near the stimulus rat during the social interest phase.

“All females spent time near the stimulus rat during the social interest phase (no-MD standard housing 242.6 ± 11.2 s, no-MD complex housing 258.5 ± 23.5 s, MD standard housing 259.2 ± 12.8 s, MD complex housing 259.2 ± 15.2 s).”

The lack of social play behavior after 3 h isolation in adolescent complex housed rats suggests a lack of motivation to engage in social play behavior due to the complex housing conditions.

“suggesting a lack of motivation to engage in social play behavior due to the complex housing conditions.”

The shorter latencies to approach novel conspecifics and objects in complex housed rats suggest a decrease in novelty anxiety.

“which suggests a decrease in novelty anxiety.”

The faster habituation of complex housed rats might explain why they engage in social play sooner with an unfamiliar play partner.

“which might explain why they engage in social play sooner with an unfamiliar play partner.”

Any model depriving pups of maternal care might be more severe for males than females.

“As a consequence, any model depriving pups of maternal care might be more severe for males than females.”

Complex housed animals seem to be differentially influenced by novel testing conditions.

“and, probably related to this, seem to be differentially influenced by novel testing conditions.”

Based on the current data, complex housing is not a suitable intervention to reverse or diminish the effects of early life adversity on social behavior.

“Finally, based on the current data, we conclude that complex housing is not a suitable intervention to reverse or diminish the effects of early life adversity on social behavior.”

Morley-Fletcher et al. (2003) were able to diminish prenatal stress-induced impairments in social play behavior in rats with physical, but not social, environmental enrichment.

“Notably, Morley-Fletcher et al. (2003) were able to diminish prenatal stress-induced impairments in social play behavior in rats with physical, but not social, environmental enrichment (Laviola et al., 2004).”

• cites Morley-Fletcher et al., 2003 sourceNot checked — no full text of the source
• cites Laviola et al., 2004 sourceNot checked — no full text of the source

The observed failure of MD rats to discriminate is not likely explained by a lack of familiarization in the social interest phase because the amount of time spent with the stimulus rat during this phase was not correlated with the DI in the social discrimination phase.

“The observed failure of MD rats to discriminate is not likely to be explained by a lack of familiarization in the social interest phase because the amount of time spent with the stimulus rat during this phase was not correlated with the DI in the social discrimination phase.”

Rats living in complex housing show a decreased HPA-axis response to a variety of stressors.

“but also show a decreased HPA-axis response to a variety of stressors (reviewed in Simpson and Kelly, 2011).”

• cites Simpson and Kelly, 2011 sourceNot checked — no full text of the source

Early life stress is known to impair (non-stressful) learning and memory.

“ELS – using a variety of models (Krugers and Joëls, 2014; Tractenberg et al., 2016) – is known to impair (non-stressful) learning and memory.”

• cites Krugers and Joëls, 2014 sourceNot checked — no full text of the source
• cites Tractenberg et al., 2016 sourceNot checked — no full text of the source

Males seem more affected by the environmental changes in this study compared to females.

“Males seem more affected by the environmental changes in this study compared to females.”

Our data support that MD-induced impairments in learning and memory also include learning and memory of social information.

“Our data are in line with these results and support that MD-induced impairments in learning and memory also include learning and memory of social information.”

• AssumptionRests on an assumption: Social discrimination relies on the ability to recognize previously encountered conspecifics and contains a short-term memory component.