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Novel models for understanding traumatic stress
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Date
2022-09-30
Authors
Lannon, Adam
Journal Title
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Publisher
University College Cork
Published Version
Abstract
Undergoing trauma, be it physical, psychological, or observed, can induce pathological alterations leading to disorders such as Post-Traumatic Stress Disorder (PTSD). PTSD is highlighted by negative cognitive alterations, behavioural changes, and interruptions in arousal and sociability. PTSD is comorbid with disorders such as anxiety and depression, gastrointestinal disturbances, pain, and the gut microbiome is hypothesized to play a role in this trauma-related disorder. Direct experience of traumatic events is the most common method of generating traumatic-stress related pathologies, however indirect exposure through witnessing another endure a traumatic event can also lead to PTSD-like symptoms. This method of traumatic transference is called secondary traumatic stress (STS). While PTSD and STS are clinically relevant, and ever-growing in importance due to the recent COVID-19 pandemic, there is still a lot to be learned about their molecular underpinning, mechanisms, and biomarkers. In order to appropriately investigate these neurobiological features of traumatic stress, valid and effective animal models are absolutely essential. Utilizing the most appropriate animal models for the representation of neuropathologies is essential for extracting critical information in the process of developing novel therapeutic options.
In chapter 2, we aim to develop the knowledge of secondary traumatic stress, we investigated whether a novel observational model, combining visceral pain, a common comorbidity of traumatic stress related disorders, and observed stress could result in a suitable phenotype. Utilizing colo-rectal distension (CRD) to induce visceral pain behaviours, we had rodents observe another rodent undergoing this procedure. These observer rodents then underwent the CRD themselves 24 hours later in order to assess whether they had visceral hypersensitivity. Indeed, it was seen that observer animals had hyperalgesia measured in visceral pain threshold and total behaviours, an impacted HPA axis, and altered neuronal activation in key brain regions. Our results suggest that this novel model was effective in producing secondary traumatic stress-like phenotypes, and would be well suited for further research into the social transference of pain and developing therapeutic options for traumatic-stress induced disorders and visceral pain comorbidity.
In chapter 3, we look at Single prolonged stress (SPS), which is a well-validated and commonly used model however there are ethical concerns that limit its widespread use. The classical SPS model involves a 2-hour restraint, immediately followed by a 20-minute forced swim, a 15-minute rest and culminates with diethyl ether exposure until loss of consciousness. Recent focus on ethical standards and interests in refining animal models has led to concerns in the usage of diethyl ether, leading us to investigate whether the model would still be effective using isoflurane as a replacement for diethyl ether. Our findings suggest that this model is effective in recapitulating a key PTSD phenotype in the contextual fear conditioning paradigm. Impaired fear learning has been repeatedly found to be a key component of PTSD phenomenology, and our model induced significantly impaired fear learning in stress rats. Further to this, we found that SPS with isoflurane caused significant reduction in learned helplessness in rodents, paired with time specific changes in corticosterone concentration. Anxiety-like behaviours also appear to be implicated by this model, with Isoflurane exposure leading to reduced anxiety-like behaviour, suggesting its potential as an adequate PTSD model.
The encouraging results from these two models of traumatic stress provide a significant interest in further studies using them. With the future intention of developing novel and effective therapeutics for undermedicated sufferers of these disorders, the hope is that these models can help provide valuable insights into the mechanisms of action behind the pathologies, illuminating potential therapeutic avenues.
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Keywords
Traumatic stress , Animal models , PTSD , Secondary traumatic stress , Visceral pain , Empathy , Modified single prolonged stress , Isoflurane
Citation
Lannon, A. 2022. Novel models for understanding traumatic stress. MSc Thesis, University College Cork.