SIBLING VARIANCE IN EARLY LIFE SOCIAL INTERACTIONS PREDICTS ADULT ANXIETY-RELATED BEHAVIOR AND PHYSIOLOGY IN RODENTS

Ragan, Christina Marie

SIBLING VARIANCE IN EARLY LIFE SOCIAL INTERACTIONS PREDICTS ADULT ANXIETY-RELATED BEHAVIOR AND PHYSIOLOGY IN RODENTS

Open Access

Author:: Ragan, Christina Marie
Graduate Program:: Neuroscience
Degree:: Doctor of Philosophy
Document Type:: Dissertation
Date of Defense:: June 16, 2011
Committee Members:: Sonia Angele Cavigelli, Dissertation Advisor/Co-Advisor
Sonia Angele Cavigelli, Committee Chair/Co-Chair
Byron C Jones, Committee Chair/Co-Chair
Victoria Braithwaite, Committee Member
Tracy Lee Langkilde, Committee Member
David John Vandenbergh, Committee Member
Keywords:: maternal behavior
exploratory behavior
sibling variance
rodent
parental care
early experience
neonatal
mother-infant relations
SERT
stress
glucocorticoid receptor
CRFR1 receptor
Abstract:: Experiences early in infancy can influence offspring development of behavior and physiology in response to stress. During this early period, variance in maternal care has been shown to affect offspring stress responses in adulthood. In rodents, rat pups of dams categorized as high-licking, tend to be more exploratory and have a reduced stress hormone response to novel stimuli in adulthood compared to offspring of low-licking dams. In addition, pups will display maternal solicitation behaviors, such as perioral contact, that prompt the dam to initiate maternal behaviors. Several studies have examined the long-term effects of varying amounts of maternal-neonate interactions on offspring development across litters, but few have investigated these interactions and effects on siblings within a litter. In the work presented here, we found that interactions with a rodent dam during the first postnatal week vary within a litter and are related to sibling differences in stress and anxiety-related behavior and physiology in adulthood. In the first and second studies with outbred Sprague-Dawley rats and inbred Agouti viable yellow mice, respectively, we found that within a litter, high-licked pups received approximately twice as many licks as their low-licked, same-sex siblings. Pups that made more maternal solicitation behaviors received more licks than siblings that did not show these behaviors as often. In adulthood, offspring that had been frequently-licked as pups were slower to approach novelty than their low-licked littermates, which was the opposite of what previous research had shown between litters. In the last study, we examined the relationships among infant-maternal interactions, adolescent and adult behavior, and behavioral and adult physiological responses to novelty and found sex-specific results. We measured mRNA expression of glucocorticoid receptors (GR) in the prefrontal cortex and hippocampus and serotonin transporter (Sert) in the brainstem, both of which are involved in stress and anxiety. Adult females that received high amounts of maternal licking as neonates expressed higher GR mRNA in the prefrontal cortex and lower corticosterone production in response to novelty compared to their low-licked sisters. Adult males that were slow to approach novelty at post-weaning and adulthood expressed lower Sert mRNA compared to their more exploratory brothers. These data imply that the pathways involved in responding to novel stimuli may be sex-specific which is similar to the marked sex-dependent responses to stress seen in humans. The studies using rodent models discussed in this dissertation have identified putative early-life predictors of adult sibling differences in responses to novel situations. Although our findings are correlational, they may shed light on possible causal relationships between the early environment and later anxiety behavior and physiology.

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