Abiola, Oluwatofunmi Ayooluwa
(2024)
Developing a translationally relevant exposure with response prevention model for obsessive compulsive disorder.
Undergraduate Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Obsessive Compulsive Disorder (OCD) is a highly prevalent and chronic psychiatric condition, marked by persistent obsessions, which are recurrent thoughts or urges, and compulsions, which are repetitive behaviors aimed at alleviating the intense anxiety these obsessions provoke. For many patients with OCD, excessive avoidance serves as their primary compulsion, with patients often going great lengths to avoid situations where they might encounter triggers of their obsessions.
Exposure with response prevention (ERP), is considered a gold standard treatment for OCD. This extinction-based therapy works by gradually exposing patients to the stimuli directly related to their obsessions while preventing patients from engaging in the compulsive behaviors they typically use to reduce obsession-evoked distress. ERP not only interrupts maladaptive behavior patterns but also fosters resilience against future compulsive urges. This has driven researchers to investigate the underlying neural circuits engaged by ERP; however, studies in humans have limited ability to dissect circuit-level mechanisms and access causality. Thus, the need for preclinical models arises.
Here, we develop a mouse model of ERP based on a novel negative reinforcement task. This task allows for temporally precise approaches to probe and manipulate the neural mechanisms underlying ERP. In this paradigm, mice are trained for seven days to avoid foot shocks by pressing a lever. Following avoidance acquisition, mice undergo either zero, one, or three days of ERP followed by three extinction tests. We found that the duration of ERP had a significant positive correlation with the extent of avoidance extinction and a significant negative correlation with freezing behavior in extinction.
Overall, this model serves as a strong framework for investigating the neural circuits underlying avoidance acquisition and extinction via ERP. Future directions involve combining this paradigm with single-photon calcium imaging to explore neural activity changes during exposure with response prevention and subsequent extinction of learned avoidance.
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Details
| Item Type: |
University of Pittsburgh ETD
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| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
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| Date: |
16 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
19 November 2024 |
| Approval Date: |
16 December 2024 |
| Submission Date: |
9 December 2024 |
| Access Restriction: |
No restriction; Release the ETD for access worldwide immediately. |
| Number of Pages: |
75 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
David C. Frederick Honors College |
| Degree: |
BPhil - Bachelor of Philosophy |
| Thesis Type: |
Undergraduate Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
obsessive compulsive disorder, exposure with response prevention, avoidance behavior, rodent model |
| Date Deposited: |
16 Dec 2024 14:04 |
| Last Modified: |
16 Dec 2024 14:04 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47214 |
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