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

Chieh V Chen,Lauren E Chaby,Israel Liberzon,Sahana Nazeer

doi:10.3389/fnbeh.2018.00247

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.

Highlights

It is commonly asserted in the literature that children and adolescents are at higher risk for trauma related psychopathology (Pynoos et al, 1987; North et al, 1994); the empirical/mechanistic evidence for this assertion is sparse and often contradictory (Green et al, 1991; Shannon et al, 1994; Tottenham and Gabard-Durnam, 2017; reviewed in Chaby et al, 2017)
We compared the effects of exposure to two trauma models, a well-established posttraumatic stress disorder (PTSD) model (SPS) and a novel predation version (SPSp), on fear associated learning in adult, mid adolescent, and early adolescent rodents
A hallmark of PTSD seen both in PTSD patients (Milad et al, 2008, 2009) and PTSD rodent models (Knox et al, 2012, 2016; George et al, 2015), was induced by exposure to two types of trauma in adulthood, but not in early or mid adolescence

Summary

Introduction

It is commonly asserted in the literature that children and adolescents are at higher risk for trauma related psychopathology (Pynoos et al, 1987; North et al, 1994); the empirical/mechanistic evidence for this assertion is sparse and often contradictory (Green et al, 1991; Shannon et al, 1994; Tottenham and Gabard-Durnam, 2017; reviewed in Chaby et al, 2017). Increased vulnerability to posttraumatic stress disorder (PTSD) following trauma in adolescence has been supported by some (Green et al, 1991) but not other studies (McFarlane, 1987; Lonigan et al, 1991). These differences stem partly from challenges inherent in the study of clinical populations, such as variation between participants in trauma type, timing, duration and prior stress history (van der Kolk, 1985; Davidson and Smith, 1990; Bokszczanin, 2007; reviewed in Schwarz and Perry, 1994). Extinction retention has been linked to activation of the ventromedial prefrontal cortex (PFC) and the hippocampus in adults, areas that still undergo development in adolescence (Meaney et al, 1985; Sowell et al, 1999), and that show reduced activity in PTSD patients (Milad et al, 2007, 2009)

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