Sex differences in stress-induced social withdrawal: Independence from adult gonadal hormones and inhibition of female phenotype by corncob bedding

Abstract

There is compelling evidence for important sex differences in behavioral and hormonal responses to psychosocial stress. Here we examined the effects of gonadal hormones on behavioral responses to social defeat stress in monogamous California mice (Peromyscus californicus). Three episodes of social defeat induced social withdrawal in intact females but not males. Gonadectomy blocked corticosterone responses to defeat in females and sensitized male corticosterone responses. However, gonadectomy had no effects on social interaction behavior, suggesting that social withdrawal is not dependent on gonadal hormones in the adult California mouse. In contrast, defeat reduced exploratory behavior in the open field test for intact but not castrated males. We also examined the effects of social defeat on social interaction behavior when California mice were raised on corncob bedding, which has estrogenic properties. In this dataset of over 300 mice, we observed that social defeat did not induce social withdrawal when females were raised on corncob bedding. This finding suggests that the use of corncob in rodent studies could mask important sex differences in the effects of stress on brain and behavior. Although gonadal hormones do not affect social withdrawal behavior in adults, our data suggest that hormones may act earlier in development to induce a more resilient social phenotype.

Influence of housing variables on the development of stress-sensitive behaviors in the rat

“…These effects have also been reported in rats [25]. The most recent paper using the California mouse as a model provides evidence, in line with our own, demonstrating that the effects of corncob bedding on adult stress-relevant behaviors appears to be generated during the postnatal, developmental window and not in adulthood [55]. An increasing body of research demonstrates that exposure to endocrine-disrupting compounds, particularly during critical developmental windows, may inuence sexually-dimorphic neuroendocrine pathways controlling reproductive behaviors.…”

Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions

“…This result mimics reports in humans that social withdrawal occurs to a greater degree in women with depression than in men [149]. Unlike the effects of defeat stress on corticosterone, there is no effect of gonadectomy on social interaction behavior [143]. Similarly, social withdrawal is observed across different stages of the estrous cycle [144••].…”

“…Acute responses of the HPA axis are more sensitive to social conflict in females than in males. Females show a significant increase in corticosterone following a resident–intruder test, and this increase is observed in both residents (winners [142]) and intruders (losers [143]). In contrast, neither male residents nor intruders show an increase in corticosterone.…”

“…1a). Castration sensitizes male corticosterone responses to defeat stress, whereas ovariectomy blocks defeat-induced increases in corticosterone in females [143]. Notably, the long-term effects of defeat stress on baseline corticosterone are quite different.…”

Rapid effects of estrogens on behavior: Environmental modulation and molecular mechanisms

“…Male rats housed on corncob bedding have reduced anxiety-like behavior and decreased slow-wave sleep compared to rats raised on wood pulp based bedding [104, 105]. In addition, corncob bedding also reduced sex differences in social withdrawal behavior following social defeat stress [106]. These results suggest that corncob may have widespread effects on brain function.…”