Prenatal stress does not alter innate novelty-seeking behavioral traits, but differentially affects individual differences in neuroendocrine stress responsivity

Abstract

SummaryExposure 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, fearand 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 to 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 anxietylike 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 prenatal stress in HR versus LR animals.

Abnormal Stress Responsivity in a Rodent Developmental Disruption Model of Schizophrenia

“…In addition, rats exposed to neonatal ventral hippocampal lesion display an attenuated increase in plasma corticosterone levels as compared with sham-lesion controls after 20 min of footshock, and this response fails to adapt after 60 min of footshock (Chrapusta et al, 2003). Similarly, the offspring of dams exposed to chronic unpredictable stress during pregnancy display an exaggerated corticosterone response to an open field test (Clinton et al, 2008). Taken together, these data suggest that USV and HPA axis responses to stress are sensitive to various developmental disruptions and that HPA axis dysregulation could contribute to other abnormal phenotypes seen in animal models of psychiatric disease.…”

Prenatal Stress and Stress Coping Style Interact to Predict Metabolic Risk in Male Rats

“…In a previous study, we found that rats genetically selected for a passive stresscoping style also displayed hyperinsulinemia when exposed to a high-fat diet, indicating that the way an individual copes with stress may further influence their risk for type 2 diabetes (11). Although PNS has been suggested to influence the stress-coping strategy of the offspring, the direction and amplitude of these changes seem highly dependent on the sex of the offspring and the type of stressor used (12)(13)(14)(15)(16)(17)(18). In the current study, we test the hypothesis that PNS and stress-coping style may interact in predicting susceptibility to adverse metabolic conditions.…”

Adolescent cocaine exposure enhances goal-tracking behavior and impairs hippocampal cell genesis selectively in adult bred low-responder rats

“…For example, bLR rats also exhibit greater anxiety- and depressive-like behaviors following stressful experiences (i.e., Calvo et al 2011; Stedenfeld et al 2011). Relative to bHRs, bLRs exhibit a higher physiological stress response (e.g., stress-induced defecation; Clinton et al 2014) and an attenuated corticosterone response to mild stressors, which appears to be a function of greater glucocorticoid receptor expression in the hippocampus (Clinton et al 2008), a finding also reported in outbred HR/LR rats (Kabbaj et al 2000). These bHR-bLR differences in HPA activity likely influence the dopamine system (e.g., Rougé-Pont et al 1998), which, in turn, could alter the response to cocaine (i.e., absence of bLR cocaine sensitization, García-Fuster et al 2010) as well as stimulus-reward learning (Flagel et al 2010, 2011).…”

“…The hippocampus is one structure that has been implicated in the differences in “emotionality” between bHRs and bLRs (e.g., Clinton et al 2008). While the hippocampus is known to be particularly sensitive to stress (e.g., Gould and Tanapat 1999), and involved in several aspects of addiction liability (Castilla-Ortega et al 2016a), including drug-context memory (e.g., Meyers et al 2006) and relapse to drug-seeking (e.g., Vorel et al 2001), the current findings are the first to investigate the relationship between hippocampal cell genesis and Pavlovian conditioned approach responses, specifically as a consequence of adolescent cocaine exposure.…”