Date Approved

3-31-2023

Embargo Period

4-6-2023

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Thomas M. Keck, Ph.D.

Committee Member 1

Lark Perez, Ph.D.

Committee Member 2

Amanda Fakira, Ph.D.

Subject(s)

Drug development; Alcoholism; Opioid abuse

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

These investigations aimed to study the effects of experimental compounds for use in treating and preventing substance use disorders, particularly opioid use disorder (OUD) and alcohol use disorder (AUD). Identifying and testing potential medications for these two diseases is critical since current FDA-approved medications are only modestly effective, and addiction continues to spread. We previously demonstrated that co-administration of morphine and MP-III-024 produced synergistic effects in hot plate and von Frey assays. This study evaluated whether MP-III-024 also produced synergistic effects in behavioral tests sensitive to the side effects of morphine. Our findings suggest that co-administration of morphine and MP-III-024 at a 1.0:0.94 ratio produced sub-additive effects in morphine-induced hyperlocomotion, behavioral disruption measure in food-maintained operant responding, and conditioned place preference. Additionally, co-administration of MP-III-024 does not affect the development of analgesic tolerance caused by chronic morphine exposure. The second part of this study investigated whether cariprazine, a D3-preferring dopamine D3R/D2R receptor partial agonist, alters alcohol self-administration in mice. Our results show a sex difference in ethanol consumption, which made evaluation of cariprazine effects difficult to detect. Further studies would be necessary to reliably conclude whether cariprazine could effectively treat AUD.

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