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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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Social interaction behavior in male and female California mice four weeks after social defeat.In the apparatus used for testing (A), the interaction zone is indicated by a blue box and the corner zones indicated by red boxes. There were no significant differences when mice were tested with an empty cage (B). Females, but not males exposed to social defeat showed reduced social interaction behavior with a novel mouse (C). Immediately after the social interaction test mice were euthanized and vaginal lavage was conducted to determine estrous cycle stage. Social defeat reduced social interaction time at different stages of the estrous cycle (D). Corticosterone levels measured immediately after social interaction testing were higher in females compared to males (E). * main effect of sex p<0.05, ** planned comparison control group versus stress group p<0.01. *** planned comparison control group versus stress group p<0.01. All data are mean±s.e.
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pone-0017405-g001: Social interaction behavior in male and female California mice four weeks after social defeat.In the apparatus used for testing (A), the interaction zone is indicated by a blue box and the corner zones indicated by red boxes. There were no significant differences when mice were tested with an empty cage (B). Females, but not males exposed to social defeat showed reduced social interaction behavior with a novel mouse (C). Immediately after the social interaction test mice were euthanized and vaginal lavage was conducted to determine estrous cycle stage. Social defeat reduced social interaction time at different stages of the estrous cycle (D). Corticosterone levels measured immediately after social interaction testing were higher in females compared to males (E). * main effect of sex p<0.05, ** planned comparison control group versus stress group p<0.01. *** planned comparison control group versus stress group p<0.01. All data are mean±s.e.

Mentions: Social interaction behavior was investigated using an apparatus consisting of a large open field (Fig. 1a, 89×63×60 cm) containing a small wire cage (14×17×14.5 cm). Each focal mouse was introduced into the open field for 3 min to habituate, and we recorded the amount of time the focal mouse spent interacting with the empty wire cage (within 8 cm, see blue box in Fig. 1A) using a video tracking system (Stoelting, Wood Dale, IL). Next an unfamiliar, same sex virgin mouse was introduced into the wire cage. For 3 min we recorded the amount of time the focal mouse spent interacting with the wire cage. We also measured time spent in the two corners opposite the wire cage (8×8 cm, Fig 1A) and total distance traveled as an estimate of total activity. After each test the arena was cleaned with 70% ethanol and dried before the next mouse was tested. Social interaction was assessed at 24 hours and 4 weeks after social defeat exposure. Different stimulus mice were used for the two tests. In between the two social interaction tests the mice were undisturbed except for routine cage changes. Immediately after testing at 4 weeks, each focal mouse was anesthetized with isoflurane and euthanized by decapitation (14:45–17:00 PST). Brains were collected immediately after testing to detect changes in phosphorylated CREB and ERK, which we have previously quantified in California mice after 7 min resident-intruder tests [30], [38]. Trunk blood was collected in heparinized tubes and centrifuged to collect plasma (see below for corticosterone assay methods). Brains were quickly removed and immersion fixed in 5% acrolein in phosphate buffered saline (PBS). Each female was lavaged post-mortem. Estrous cycle stage was determined by assessing the presence of leukocytes, nucleated epithelial cells, and/or cornified cells [30], [39].


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)

Social interaction behavior in male and female California mice four weeks after social defeat.In the apparatus used for testing (A), the interaction zone is indicated by a blue box and the corner zones indicated by red boxes. There were no significant differences when mice were tested with an empty cage (B). Females, but not males exposed to social defeat showed reduced social interaction behavior with a novel mouse (C). Immediately after the social interaction test mice were euthanized and vaginal lavage was conducted to determine estrous cycle stage. Social defeat reduced social interaction time at different stages of the estrous cycle (D). Corticosterone levels measured immediately after social interaction testing were higher in females compared to males (E). * main effect of sex p<0.05, ** planned comparison control group versus stress group p<0.01. *** planned comparison control group versus stress group p<0.01. All data are mean±s.e.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3045459&req=5

pone-0017405-g001: Social interaction behavior in male and female California mice four weeks after social defeat.In the apparatus used for testing (A), the interaction zone is indicated by a blue box and the corner zones indicated by red boxes. There were no significant differences when mice were tested with an empty cage (B). Females, but not males exposed to social defeat showed reduced social interaction behavior with a novel mouse (C). Immediately after the social interaction test mice were euthanized and vaginal lavage was conducted to determine estrous cycle stage. Social defeat reduced social interaction time at different stages of the estrous cycle (D). Corticosterone levels measured immediately after social interaction testing were higher in females compared to males (E). * main effect of sex p<0.05, ** planned comparison control group versus stress group p<0.01. *** planned comparison control group versus stress group p<0.01. All data are mean±s.e.
Mentions: Social interaction behavior was investigated using an apparatus consisting of a large open field (Fig. 1a, 89×63×60 cm) containing a small wire cage (14×17×14.5 cm). Each focal mouse was introduced into the open field for 3 min to habituate, and we recorded the amount of time the focal mouse spent interacting with the empty wire cage (within 8 cm, see blue box in Fig. 1A) using a video tracking system (Stoelting, Wood Dale, IL). Next an unfamiliar, same sex virgin mouse was introduced into the wire cage. For 3 min we recorded the amount of time the focal mouse spent interacting with the wire cage. We also measured time spent in the two corners opposite the wire cage (8×8 cm, Fig 1A) and total distance traveled as an estimate of total activity. After each test the arena was cleaned with 70% ethanol and dried before the next mouse was tested. Social interaction was assessed at 24 hours and 4 weeks after social defeat exposure. Different stimulus mice were used for the two tests. In between the two social interaction tests the mice were undisturbed except for routine cage changes. Immediately after testing at 4 weeks, each focal mouse was anesthetized with isoflurane and euthanized by decapitation (14:45–17:00 PST). Brains were collected immediately after testing to detect changes in phosphorylated CREB and ERK, which we have previously quantified in California mice after 7 min resident-intruder tests [30], [38]. Trunk blood was collected in heparinized tubes and centrifuged to collect plasma (see below for corticosterone assay methods). Brains were quickly removed and immersion fixed in 5% acrolein in phosphate buffered saline (PBS). Each female was lavaged post-mortem. Estrous cycle stage was determined by assessing the presence of leukocytes, nucleated epithelial cells, and/or cornified cells [30], [39].

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