Neuropeptides in the Bed Nucleus Stria Terminalis: Implications in Chronic Stress
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Authors
Normandeau, Catherine
Date
Type
thesis
Language
eng
Keyword
Neurotensin , Corticotropin releasing factor , Dynorphin , Chronic Stress , Anxiety , Synaptic plasticity
Alternative Title
Abstract
For the last 20-30 years, new discovery of pharmacological treatment for psychiatric disorders has been stagnant despite a pressing need to find alternative therapies for patients that are treatment-resistant to the current medication. Neuropeptides are powerful modulators of neural activity that robustly influence a wide-range of behaviours. Notably, their expression profiles and subsequent function can be altered in some mental health illnesses such as anxiety disorders. However, neuropeptides are rarely studied in clinically relevant contexts. Consequently, there is currently a lack of understanding of how they may predict or contribute to certain pathological states. Pre-clinical models in rodents are useful tools to investigate this. The chronic unpredictable stress (CUS) is one model that mimics the every day stressors that can lead to pathologies in humans. Here, we hypothesize that neuropeptide modulation will be altered after male rats are exposed to CUS resulting in changes in behaviour. Specifically, we look at the effect of neuropeptides in the oval bed nucleus of the stria terminalis (ovBNST), a brain area sensitive to energy homeostasis and the anticipation of aversive stressors. We found that endogenously released neuropeptides robustly modulate both excitatory and inhibitory transmission. Interestingly, CUS altered neuropeptides regulation of synaptic transmission whereby one neuropeptide (neurotensin (NT)) became the dominant modulator of inhibitory transmission. To investigate whether this had behavioural consequences, we pharmacologically blocked NT in the ovBNST and tested rats in the elevated plus maze (EPM) and forced swim test (FST). We observed changes only in exploratory behaviour in the CUS rats where blockage of NT increased time spent in the open arm suggesting a reduction in anxiety-like behaviour. Lastly, knowing that modulation of inhibitory transmission is specifically changed with CUS, we examined how neuropeptides may influence the main inhibitory inputs to the ovBNST: the central amygdala (CeA). We found that NT and dynorphin antagonistically modulate CeA-to-ovBNST inputs. Whether this modulation changes in different conditions or animal state remains elusive. Overall, multiple neuropeptides regulate the activity of ovBNST neurons that is dysregulated following a chronically stressful experience (i.e., CUS) but whether these changes observed are adaptive or maladaptive has yet to be determined.
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Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.
Queen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canada
ProQuest PhD and Master's Theses International Dissemination Agreement
Intellectual Property Guidelines at Queen's University
Copying and Preserving Your Thesis
This publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.