Repetitive blast promotes chronic aversion to neutral cues encountered in the peri-blast environment

• Published in: bioRxiv
• Main Authors: Schindler, Abigail G, Terry, Garth E, Wolden-Hanson, Tami, Cline, Marcella, Park, Michael, Lee, Janet, Yagi, Mayumi, Meabon, James S, Raskind, Murray M, Peskind, Elaine R, Phillips, Paul Em, Cook, David G
• Format: Paper
• Language: English
• Published: Cold Spring Harbor Cold Spring Harbor Laboratory Press 05.07.2020; Cold Spring Harbor Laboratory
• Edition: 1.2
• Subjects: Animal models; Aversion; Body weight loss; Comorbidity; Morbidity; Neuroscience; Post traumatic stress disorder; Traumatic brain injury; PTSD; traumatic brain injury; stress; veteran; blast
• ISSN: 2692-8205; 2692-8205
• DOI: 10.1101/2020.02.11.935718

Repetitive mild traumatic brain injury (mTBI) has been called the signature injury of military Servicemembers in the Iraq and Afghanistan wars and is highly comorbid with posttraumatic stress disorder (PTSD). Correct attribution of adverse blast-induced mTBI and/or PTSD remains challenging. Preclinical research using animal models can provide important insight into the mechanisms by which blast produces injury and dysfunction but only to the degree by which such models reflect the human experience. Avoidance of trauma reminders is a hallmark of PTSD, here we sought to understand whether a mouse model of blast reproduces this phenomenon, in addition to blast-induced physical injuries. Drawing upon well established work from the chronic stress and Pavlovian conditioning literature, we hypothesized that, even while anesthetized during blast exposure, environmental cues encountered in the peri blast environment could be conditioned to evoke aversion/dysphoria and reexperiencing of traumatic stress. Using a pneumatic shock tube that recapitulates battlefield-relevant open-field blast forces, we provide direct evidence that stress is inherent to repetitive blast exposure, resulting in chronic aversive/dysphoric-like responses to previous blast-paired cues. The results in this report demonstrate that, while both single and repetitive blast exposures produce acute stress responses (weight loss, corticosterone increase), only repetitive blast exposure also results in co-occurring aversive/dysphoric-like stress responses. These results extend appreciation of the highly complex nature of repetitive blast exposure; and lend further support for the potential translational relevance of animal modeling approaches currently used by multiple laboratories aimed at elucidating the mechanisms (both molecular and behavioral) of repetitive blast exposure. Competing Interest Statement The authors have declared no competing interest.