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Sex differences in social interaction behavior following social defeat stress in the monogamous California mouse (Peromyscus californicus).

Trainor BC, Pride MC, Villalon Landeros R, Knoblauch NW, Takahashi EY, Silva AL, Crean KK - PLoS ONE (2011)

Bottom Line: Social defeat reduced social interaction responses in females but not males.This effect of defeat was not observed in males.The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California Davis, Davis, California, United States of America. bctrainor@ucdavis.edu

ABSTRACT
Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior.

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Immunostaining for phosphorylated CREB in female (A, B, C) and male (D,E, F) California mice after social interaction tests.Mice were exposed to three control or social defeat episodes. Social defeat increased the number of pCREB positive cells in females but not males in the NAc shell (C) and core (F). Control males generally had higher pCREB cell counts than control females. † Mann-Whitney sex difference in controls p<0.05, *, **, Mann-Whitney effect of stress p<0.05, p<0.01 respectively. All data are mean±s.e. Anterior commissure, ac. Scale bars = 100 µm.
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pone-0017405-g004: Immunostaining for phosphorylated CREB in female (A, B, C) and male (D,E, F) California mice after social interaction tests.Mice were exposed to three control or social defeat episodes. Social defeat increased the number of pCREB positive cells in females but not males in the NAc shell (C) and core (F). Control males generally had higher pCREB cell counts than control females. † Mann-Whitney sex difference in controls p<0.05, *, **, Mann-Whitney effect of stress p<0.05, p<0.01 respectively. All data are mean±s.e. Anterior commissure, ac. Scale bars = 100 µm.

Mentions: In the NAc females exposed to defeat had more pCREB positive cells in the shell (Fig. 4C, Mann-Whitney U, p<0.05) and core (Fig. 4F, p<0.05) immediately following social interaction testing compared to control females. In males there was no significant effect of stress on pCREB positive cells in either the NAc shell (Fig. 4C) or NAc core (Fig. 4F). Control males had more pCREB positive cells than control females in the NAc shell (Fig. 4C, Mann-Whitney, p<0.01). Across all mice, pCREB positive cells in the shell were negatively correlated with time spent interacting with the target mouse (Fig. 5, Spearman ρ = −0.37, p<0.05). There were no significant correlations between time spent interacting with the target mouse and pCREB positive cells in the core (overall or within males or females). There were no effects of stress on pERK positive cells in the NAc (Fig. 6), but control males had more pERK positive cells than control females in the NAc shell (Fig. 6B, Mann-Whitney, p<0.05).


Sex differences in social interaction behavior following social defeat stress in the monogamous California mouse (Peromyscus californicus).

Trainor BC, Pride MC, Villalon Landeros R, Knoblauch NW, Takahashi EY, Silva AL, Crean KK - PLoS ONE (2011)

Immunostaining for phosphorylated CREB in female (A, B, C) and male (D,E, F) California mice after social interaction tests.Mice were exposed to three control or social defeat episodes. Social defeat increased the number of pCREB positive cells in females but not males in the NAc shell (C) and core (F). Control males generally had higher pCREB cell counts than control females. † Mann-Whitney sex difference in controls p<0.05, *, **, Mann-Whitney effect of stress p<0.05, p<0.01 respectively. All data are mean±s.e. Anterior commissure, ac. Scale bars = 100 µm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045459&req=5

pone-0017405-g004: Immunostaining for phosphorylated CREB in female (A, B, C) and male (D,E, F) California mice after social interaction tests.Mice were exposed to three control or social defeat episodes. Social defeat increased the number of pCREB positive cells in females but not males in the NAc shell (C) and core (F). Control males generally had higher pCREB cell counts than control females. † Mann-Whitney sex difference in controls p<0.05, *, **, Mann-Whitney effect of stress p<0.05, p<0.01 respectively. All data are mean±s.e. Anterior commissure, ac. Scale bars = 100 µm.
Mentions: In the NAc females exposed to defeat had more pCREB positive cells in the shell (Fig. 4C, Mann-Whitney U, p<0.05) and core (Fig. 4F, p<0.05) immediately following social interaction testing compared to control females. In males there was no significant effect of stress on pCREB positive cells in either the NAc shell (Fig. 4C) or NAc core (Fig. 4F). Control males had more pCREB positive cells than control females in the NAc shell (Fig. 4C, Mann-Whitney, p<0.01). Across all mice, pCREB positive cells in the shell were negatively correlated with time spent interacting with the target mouse (Fig. 5, Spearman ρ = −0.37, p<0.05). There were no significant correlations between time spent interacting with the target mouse and pCREB positive cells in the core (overall or within males or females). There were no effects of stress on pERK positive cells in the NAc (Fig. 6), but control males had more pERK positive cells than control females in the NAc shell (Fig. 6B, Mann-Whitney, p<0.05).

Bottom Line: Social defeat reduced social interaction responses in females but not males.This effect of defeat was not observed in males.The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychology, University of California Davis, Davis, California, United States of America. bctrainor@ucdavis.edu

ABSTRACT
Stressful life experiences are known to be a precipitating factor for many mental disorders. The social defeat model induces behavioral responses in rodents (e.g. reduced social interaction) that are similar to behavioral patterns associated with mood disorders. The model has contributed to the discovery of novel mechanisms regulating behavioral responses to stress, but its utility has been largely limited to males. This is disadvantageous because most mood disorders have a higher incidence in women versus men. Male and female California mice (Peromyscus californicus) aggressively defend territories, which allowed us to observe the effects of social defeat in both sexes. In two experiments, mice were exposed to three social defeat or control episodes. Mice were then behaviorally phenotyped, and indirect markers of brain activity and corticosterone responses to a novel social stimulus were assessed. Sex differences in behavioral responses to social stress were long lasting (4 wks). Social defeat reduced social interaction responses in females but not males. In females, social defeat induced an increase in the number of phosphorylated CREB positive cells in the nucleus accumbens shell after exposure to a novel social stimulus. This effect of defeat was not observed in males. The effects of defeat in females were limited to social contexts, as there were no differences in exploratory behavior in the open field or light-dark box test. These data suggest that California mice could be a useful model for studying sex differences in behavioral responses to stress, particularly in neurobiological mechanisms that are involved with the regulation of social behavior.

Show MeSH
Related in: MedlinePlus