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Early life experience and social status in the laboratory rat: Addressing causal questions from social epidemiology

  • Author(s): Saxton, Katherine Blair
  • Advisor(s): Catalano, Ralph
  • et al.
Abstract

Social position and early life environment consistently correlate with health and disease in human populations and animal models. Social epidemiology has succeeded at describing relationships between social factors and health outcomes; however, fundamental questions of etiology and causation persist. Studies on the health effects of relative social position face complex challenges including the clustering of risk factors, the inability to adequately control confounders, questions of temporality, and difficulty in measuring complicated social environments.

One central hypothesis concerning the link between social status and health focuses on differential exposure and response to stressors, suggesting that the stress of low social status throughout the lifecourse chronically activates biological stress responses, increasing risk of disease. Insight into the biological underpinnings of these relationships in humans can be furthered by innovative approaches to social epidemiology, including the application of carefully designed animal studies.

In Chapter 1, the relationship between social status and biological and behavioral outcomes is examined in group-housed male laboratory rats. Rats matched on weight and maternal behavior at weaning form a social hierarchy in their homecage without intervention. Results demonstrate a social gradient in endocrine response to acute stress, exploratory behaviors, and cognitive performance. Subordinate rats showed a blunted corticosterone response to acute stress, lowest levels of exploratory behavior, and poorest cognitive performance in the homecage. Stress of social subordination likely causes the observed differences. This study improves on animal models of social hierarchy by fully characterizing and controlling for early life environment. Results demonstrate that laboratory rats can be used as a model for social hierarchy in humans.

Chapter 2 examines the interaction between early life experience and adult social position, comparing laboratory rats and humans. For the human study, college students reported on their current subjective social status and family home ownership during their childhood. The rat study used the model of social hierarchy described in Chapter 1. An interaction between early life experience and adult social status was identified in both species. Rats and humans who experienced early life adversity (low levels of maternal care in rats, low childhood socioeconomic status in humans) represented both the highest and lowest levels of IL-6 in adulthood, depending on their social status as young adults. Therefore, early adversity may not have a monotonically negative effect on later life health, but appears to alter responsiveness to later exposures.

Chapter 3 examined the formation of social hierarchies within cages of group-housed male laboratory rats. Rats were housed together at weaning and competed for access to chocolate and water within their homecage throughout the juvenile, adolescent, and adult periods. Late adolescence (postnatal day 45) emerged as a crucial time for hierarchy development. All cages showed a distinct hierarchy at 45 days of age, and half of the groups maintained stable hierarchies from postnatal day 45 into adulthood. Results suggest that careful consideration of developmental windows would improve studies of social status in animal models.

This approach improves on translational research by providing an animal model specifically designed to address public health questions. Results of these studies suggest that an animal model of social hierarchy can inform questions from social epidemiology and further the understanding of relationships between social experience and health in human populations.

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