Date of Award

5-2022

Document Type

Thesis

Degree Name

Master of Science (MS)

College/School

College of Science and Mathematics

Department/Program

Biology

Thesis Sponsor/Dissertation Chair/Project Chair

Elena Petroff

Committee Member

Vladislav Snitzarev

Committee Member

Herman Fernandes

Abstract

Background: Post-traumatic stress disorder (PTSD) is a complex and multifaceted neurological disorder that is characterized by intrusive thoughts, avoidance behaviors, alterations in cognition and mood, and alterations in arousal and reactivity. Current studies utilize stress paradigms to mimic behavioral symptoms and neurobiological changes associated with PTSD. The project aims to instead utilize the kappa opioid system and three distinct Kappa Opioid Receptorspecific compounds (Salvinorin A, U50,488, and nor-BNI) to induce these changes. Pharmacokinetic analysis of Salvinorin A and U50,488 revealed a time of peak plasma concentration (Tmax) of 0.25 hours in both groups. 3-Chamber Social Novelty testing revealed a significant decrease in sociability and social novelty preference in the Salvinorin A group. Elevated Plus Maze testing revealed a significant increase in anti-anxiety behavior in the U50,488 groups and a significant decrease in locomotion for both the Salvinorin A and U50,488 groups. Fear Conditioning showed a significant deficit in contextual fear memory for the Salvinorin A and U50,488 groups and no significant deficit in cued memory for any group.

Importance: Current PTSD paradigms require weeks of training and conditioning to elicit a PTSD-like phenotype. This comes at a cost of time and money to the researcher, and conditioning requires chronically subjecting the test subject to trauma. The development of a more acute and less invasive PTSD model would be beneficial as it would allow more research to be done in a shorter amount of time while providing a more humane experience for the animal. Furthermore, the development of a drug-induced model would provide better information on the biological mechanisms in play, and provide new pharmaceutical targets for treatment.

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