High novelty-seeking rats are resilient to negative physiological effects of the early life stress

Abstract

Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1–14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs’ already high physiological response to stress – stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs’ (but not bHRs’) neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals’ response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

Inborn stress reactivity shapes adult behavioral consequences of early-life maternal separation stress

“…In our previous study we evaluated the effects of MS on behavior and endocrine function in the selectively-bred Low (bLR) and High (bHR) responder rats [3]. These rats were bred from the Sprague-Dawley strain and show striking differences in their depressive- and anxiety-like behavior, with bLRs showing a profile similar to the WKY rats and bHRs resembling Wistar rats [5].…”

“…While MS did not induce changes in the bLR/bHR behaviors on the OFT and FST, their endocrine responses were differentially impacted with the bLRs manifesting an augmentation of adrenocorticotropic hormone secretion in response to an anxiogenic stimulus (i.e. exposure to the light/dark box) and bHRs showing its blunting [3]. While beyond the scope of the current study, it will be important to determine the impact of MS on the HPA axis activity in the WKY and Wistar rats given that the activity of this system has the potential to shape to depression and anxiety [9].…”

“…Male/female pairs were mated for 14 days, and at birth (P0) litters were randomly assigned to one of two groups: (a) neonatal handling group or (b) MS group (n = 4 litters/group/strain). Litters assigned to the MS group and neonatal handling group were separated from their dam daily for 180 min and 15 min, respectively, between 8:30 a.m. – 12:00 p.m. from P1-P14 as previously described [3]. Dams remained in the home cages while separated litters were transferred to a different room in a small cage placed on a heating pad (∼37°C).…”

Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice

“…There is also evidence that some behavioral phenotypes confer resilience; for example, high noveltyseeking rats are more resilient against maternal separation, and do not exhibit the typical negative behavioral and neuroendocrine consequences [54]. Others have found that epigenetic mechanisms mediate the variable effects of maternal separation on mice of different genetic backgrounds [55].…”

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).…”