Date Approved

1-20-2021

Embargo Period

1-22-2021

Document Type

Thesis

Degree Name

M.S. Pharmaceutical Sciences

Department

Chemistry & Biochemistry

College

College of Science & Mathematics

Advisor

Keck, Thomas M.

Committee Member 1

Grinias, James

Committee Member 2

Fischer, Bradford D.

Keywords

Addiction, Alcohol use disorder, CB1 negative allosteric modulator, condition place preference, Dopamine D4 antagonist, Two bottle choice

Subject(s)

Alcoholism--Treatment; Drug development

Disciplines

Pharmacy and Pharmaceutical Sciences

Abstract

The USA faces $220 billion economic loss and eighty thousand deaths per year due to alcohol abuse while affecting more than 15 million people, making it the third largest life-style related cause of death. The U.S. FDA has approved four medications namely, disulfiram, acamprosate, oral naltrexone, and injectable long-acting naltrexone. These existing drugs are trashed with side effects, have a low success rate, indicating a demand for new potential drugs. We studied the effects of the CB1 negative allosteric modulator, PSNCBAM-1, and the dopamine D4 receptor antagonist, L-745,870 in mouse models of alcohol addiction. PSNCBAM-1 did not significantly reduce CPP for 2.0 g/kg ethanol or alter locomotor activity, but its dose-dependently attenuated oral ethanol self-administration at the dose of 30 mg/kg. 18 and 30 mg/kg PSNCBAM-1 significantly reduced self-administration of palatable food reward. These results suggest, PSNCBAM-1 produces a non-specific anhedonic effect that may preclude its use in AUD. L-745,870 did not significantly affect conditioned place preference for 2.0 g/kg ethanol, ethanol self-administration, locomotor activity in an open field, or co-ordination in the rotarod test. These results suggest that D4R antagonism does not alter the rewarding value of ethanol.

Download

Share

COinS