Effects of Trauma in Adulthood and Adolescence on Fear Extinction and Extinction Retention: Advancing Animal Models of Posttraumatic Stress Disorder

Abstract

Evidence for and against adolescent vulnerability to posttraumatic stress disorder (PTSD) is mounting, but this evidence is largely qualitative, retrospective, or complicated by variation in prior stress exposure and trauma context. Here, we examine the effects of development on trauma vulnerability using adult post-natal (PN) day 61, early adolescent (PN23) and mid adolescence (PN34) rats and two types of trauma: an established animal model of PTSD, single prolonged stress (SPS), and a novel composite model—SPS predation (SPSp) version. We demonstrate that early and mid adolescent rats are capable of fear conditioning and fear extinction, as well as extinction retention. Our results also demonstrate that both types of trauma induced a deficit in the retention of fear extinction in adulthood, a hallmark of PTSD, but not after early or mid adolescence trauma, suggesting that adolescence might convey resilience to SPS and SPSp traumas. Across all three life stages, the effects of SPS exposure and a novel predation trauma model, SPSp, had similar effects on behavior suggesting that trauma type did not affect the likelihood of developing PTSD-like symptoms, and that SPSp is a predation-based trauma model worth exploring.

Cognitive Flexibility Training Improves Extinction Retention Memory and Enhances Cortical Dopamine With and Without Traumatic Stress Exposure

“…Future studies elucidating the mechanism by which cognitive flexibility buffers effects of trauma should investigate sex-specific effects as well as effects on suites of psychopathological symptoms that have been characterized across the sexes. Although a main effect of SPS was not detected in the current experiment, effects of SPS on extinction retention freezing behavior were detected over time, and extensive prior evidence demonstrates that SPS (and PTSD) impair extinction retention (Milad et al, 2008, 2009; Knox et al, 2012, 2016; Chen et al, 2018). Thus, the authors feel the results demonstrate that cognitive flexibility training has the potential to be a meaningful non-invasive strategy to enhance wellbeing in the context of trauma and vulnerable populations.…”

“…Prior research has demonstrated that SPS-induced neuroendocrine effects, including HPA negative feedback and glucocorticoid receptor mRNA expression, are only evident after SPS following a 7-day quiescent period (Liberzon et al, 1997, 1999), reflecting the 30-day post-trauma delay required before PTSD can be diagnosed in humans (reviewed in Cahill and Pontoski, 2005). Thus, it is often included in the SPS model to isolate rodents for a 7-day quiescent period to prevent social buffering, and to integrate lasting effects of the trauma exposure (Knox et al, 2012; Chen et al, 2018; George et al, 2018). As brief periods of isolation in adulthood can also have neuroendocrine effects, control rats were also isolated to account for potential effects of housing (Raz and Berger, 2010).…”

Developmental regulation of fear memories by an obesogenic high-saturated fat/high-sugar diet

“…In light of findings that show changes in fear and stress reactivity during the transition into and out of adolescence (Chen et al, 2018;Pattwell et al, 2012;2013;Spear, 2000), we used a neurodevelopmental approach to understand how WD consumption alters the trajectories of fear extinction. By using a conditioningreconditioning paradigm, we aimed to examine fear responses to immediate extinction as well as long-term fear extinction memories, spontaneous recovery, and fear memory recall.…”

Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats

“…In SPS, rats are exposed to three stressors in succession followed by isolation for 7-days [additional detail in supplementary methods and 44,64,65 ]. Briefly, rats were restrained for 2 h, then forced to swim (23-24 °C) in a 68 × 56 × 45 cm opaque plastic container in groups of 6-8 for 20 min.…”