Summary

Exposure to stress during prenatal or early postnatal life can dramatically impact adult behavior and neuroendocrine function. We recently began to selectively breed Sprague-Dawley rats for high (high responder, HR) and low (low responder, LR) novelty-seeking behavior, a trait that predicts a variety of differences in emotional reactivity, including differences in neuroendocrine stress response, fear- and anxiety-like behavior, aggression, and propensity to self-administer drugs of abuse. We evaluated genetic–early environment interactions by exposing HR- and LR-bred animals to prenatal stress (PS) from pregnancy day 3–20, hypothesizing that PS exposure would differentially impact HR versus LR behavior and neuroendocrine reactivity. We evaluated novelty-induced locomotion, anxiety-like behavior, and corticosterone stress response in weanling (25-day-old) and adult HR–LR stressed and control males. Exposure to PS did not alter HR–LR differences in locomotion, but did impact anxiety-like behavior, specifically in LR animals. Surprisingly, LR animals exposed to PS exhibited less anxiety than LR controls. HR rats were not affected by PS, with both stress and control groups showing low levels of anxiety. PS differentially impacted neuroendocrine stress reactivity in young versus adult HR–LR animals, leading to an exaggerated corticosterone response in LR pups compared to LR controls, while HRs pups were unaffected. In contrast, exposure to PS produced an exaggerated stress response in HR adults, compared to HR controls, while LR animals were not significantly affected. These findings highlight how genetic predisposition may shape individual's response to early life stressors, and furthermore, show that a history of early life stress may differentially impact an organism at different points in life. Future work will explore neural mechanisms which underlie the different behavioral and neuroendocrine consequences of PS in HR versus LR animals.