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.

Highlights

  • Stressful life experiences are known to contribute to the development of mood disorders [1], yet the mechanisms that translate these stressful experiences into behavior are poorly understood

  • We examined phosphorylated CREB and phosphorylated extracellular-signal regulated kinase expression in the ‘‘extended amygdala’’ as indirect markers of cellular activity

  • Anatomical and functional similarities among the amygdala, bed nucleus of the stria terminalis (BNST), and nucleus accumbens (NAc) shell have led some research groups to refer to these regions as the ‘‘extended amygdala’’ [20]. Nuclei within this circuit are known to mediate behavioral responses induced by social defeat [8,21,22], so we examined indirect markers of brain activity in these nuclei following social interaction testing

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Summary

Introduction

Stressful life experiences are known to contribute to the development of mood disorders [1], yet the mechanisms that translate these stressful experiences into behavior are poorly understood. The social defeat model induces a constellation of long lasting behavioral responses in many species that mimic aspects of psychiatric disorders [4]. The rationale for this model is that social conflict can be a precipitating factor for many mood disorders [5,6]. The most commonly studied laboratory rodents have low levels of female-female aggression, so it has been difficult to study female responses to defeat (but see [14]) This is problematic because depression and anxiety disorders are more common in women than men [15,16]. We describe data collected from the monogamous California mouse (Peromyscus californicus), in which the social defeat paradigm is examined in both males and females

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