Date of Award

2025

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Boyd R. Rorabaugh

Second Advisor

Dr. Daniel J. Morgan

Third Advisor

Dr. Michael D. Hambuchen

Abstract

Stimulant use disorder is a significant health and social crisis. Psychosocial therapies are currently the standard of care for stimulant use disorder (SUD). Several prescription medications (serotonin-selective reuptake inhibitors, long-acting amphetamines, modafinil, and others.) have been used “off-label” to treat use disorder to cocaine, methamphetamine, and other stimulants. However, existing pharmacotherapies are associated with a high rate of relapse, and none of them have met the efficacy requirements necessary for FDA approval. Thus, there is a tremendous need for the identification of novel molecular targets and new pharmacotherapies for the treatment of use disorders of these stimulants. Previous work suggests that the regulator of G protein 6 (RGS6) may be involved in signaling pathways that lead to addiction. This study was performed using drugs such as cocaine, methamphetamine, and morphine, and we found that the knockout of RGS6 showed rewarding effects of cocaine, but there was no effect of methamphetamine and morphine. When cumulative dose-response tests were performed, we found that RGS6 knockdown enhanced the hypothermic effect in a sex-dependent manner.

Subject(s)

Substance abuse.

Drug addiction -- Treatment.

Stimulants -- Substance use -- Treatment.

Stimulants -- Substance use -- Prevention.

Cocaine.

Methamphetamine.

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