Date Approved

9-28-2021

Embargo Period

9-30-2022

Document Type

Thesis

Degree Name

Master of Science in Pharmaceutical Sciences

Department

Chemistry and Biochemistry

College

College of Science & Mathematics

Advisor

Thomas M. Keck, Ph.D.

Committee Member 1

James P. Grinias, Ph.D.

Committee Member 2

Martin O. Job, Ph.D.

Keywords

Alcohol Use Disorder (AUD), CAB-01-019, CD-1 mice, Morphine, MP-III-024, Opioid Use Disorder (OUD)

Subject(s)

Drug development; Drugs--Testing

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

Opioid use disorder (OUD) and alcohol use disorder (AUD) are pressing public health problems in the United States that require new pharmacotherapies to be explored. Current FDA-approved treatment options for these two disorders are only moderately effective. Thus, there is a demand for the identification of new targets for drug development. Previous research initiatives have shown that when morphine is co-administered with the novel imidazodiazepine, MP-III-024, synergistic effects in models of analgesia and antinociception are produced. Our research efforts were concerned with understanding if morphine in combination with MP-III-024 produced synergistic effects in measures of undesirable pharmacological responses: opioid side effects. The results of our operant self-administration tests demonstrated that MP-III-024 does not enhance morphine induced disruptions; and in models of locomotor function, our 1.0:0.94 morphine:MP-III-024 ratio demonstrated a statistically significant subadditive (anti-synergistic) effect. With these findings, we now know that morphine and MP-III-024 are not universally synergistic. Concerning AUD, the dopamine D4 receptor (D4R) full antagonist, CAB-01-019, was studied through palatable food self-administration testing. Our results showed that CAB-01-019 did not significantly reduce behavioral responses at any of the three tested doses (10, 17.8, and 30 mg/kg). These palatable food self-administration tests with CAB-01-019 will serve as a critical control for future alcohol tests.

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