DOI
https://doi.org/10.25772/AADW-SX59
Defense Date
2023
Document Type
Thesis
Degree Name
Master of Science
Department
Biochemistry
First Advisor
Matthew Banks
Second Advisor
Tomazs Kordula
Third Advisor
Carmen Sato-Bigbee
Abstract
The current opioid epidemic in the United States has steadily increased over the past several years and despite the availability of three Food and Drug Administration (FDA) approved medications available for opioid use disorder (OUD) treatment. These OUD medications are the full mu agonist methadone, the partial mu agonist buprenorphine, and the opioid antagonist naltrexone. Although these OUD medications are effective in some patients, undesirable effects limit patient compliance and retention rates. Thus, there is a need for more diverse OUD treatment options. Toward this goal, mu-opioid receptor agonists that have lower efficacy than buprenorphine but higher efficacy than naltrexone are of interest as one approach to retain clinical treatment effectiveness with fewer undesirable effects. This dissertation evaluated a low-efficacy mu agonist NAT as a candidate OUD treatment using a preclinical heroin-vs-food choice procedure that has shown strong translational predictive validity. Chapter II describes experiments determining the effectiveness of NAT to decrease heroin-vs-food choice in male and female Sprague Dawley rats. In addition, abuse liability assessment of NAT was determined using an intravenous drug self-administration procedure. Repeated NAT treatment caused dose-dependent decreases in percent heroin choice and produced behavioral reallocation of behavior from drug to non-drug reinforcer similar to results with naltrexone and buprenorphine. NAT also functions as a reinforcer in rats suggesting some abuse liability in humans. Overall, the results described in this thesis suggest that NAT has potential clinical utility as an effective candidate OUD treatment and further clinical studies are warranted.
Rights
© The Author
Is Part Of
VCU University Archives
Is Part Of
VCU Theses and Dissertations
Date of Submission
4-28-2023