Date of Award
Spring 5-1-2025
Document Type
Thesis (Ph.D.)
Department or Program
Integrative Neuroscience
First Advisor
Wilder Doucette, MD, PhD
Second Advisor
Paul Holtzheimer, MD
Abstract
Severe trauma exposure related to traumatic brain injury (TBI) or psychiatric disorders like post-traumatic stress disorder (PTSD) leads to neurobehavioral and physiological impairments that reduce the quality of life of individuals and remain difficult to treat with current therapeutic options. Further, these conditions are highly comorbid, notably in PTSD with blast-traumatic brain injury (bTBI) commonly experienced by military members via explosive forces, leading to complex and heterogenous outcomes. To address this, preclinical models have been developed to recapitulate aspects of TBI and PTSD. This thesis utilizes two such models in rats, bTBI and the single prolonged stress (SPS) model for PTSD, to elucidate chronic consequences and to evaluate emerging interventions. Chapter 1 demonstrates that a model of bTBI produces behavioral dysfunction at chronic time points across domains (i.e., anxiety and depressive-like, motivational, and fear phenotypes) and corresponding changes in brain structure and function, revealed through neural oscillations and neuroimaging. Chapter 2 evaluates the efficacy of 3,4-methylenedioxymethamphetamine (MDMA) to reduce expression of cued fear behavior in bTBI rats. This revealed that MDMA as an adjunct to re-exposure of conditioned trauma, akin to exposure therapy, had efficacy for reducing fear behavior and resulted in acute and persisting oscillatory changes related to MDMA. In Chapter 3, the SPS model was used to investigate potential stress hormonal changes and anxiety-like and social behaviors related to PTSD, with and without cue re-exposure. These behavioral and physiological impairments were not revealed at the time points tested, showing this commonly reported protocol may need modification to serve as a robust and intervenable model for PTSD. Collectively, these multimodal studies advance our understanding of trauma exposure on chronic neurobehavioral outcomes and serve to guide emerging interventions for bTBI and PTSD.
Recommended Citation
McGuier, Moriah E., "From Trauma to Treatment: Chronic Neurobehavioral Consequences and Emerging Treatments" (2025). Dartmouth College Ph.D Dissertations. 396.
https://digitalcommons.dartmouth.edu/dissertations/396
Included in
Behavior and Behavior Mechanisms Commons, Translational Medical Research Commons, Trauma Commons
