TAAR1 Agonists for the Treatment of Stimulant Use Disorder

About This Grant

PROJECT SUMMARY / ABSTRACT Cocaine use disorder (CUD) is a serious public health concern in the United States. Approximately 0.5% of the US population have CUD, and these people are more prone to death, particularly by overdose, suicide, and cardiovascular events. CUD treatment focuses on psychological therapies, which are expensive and only moderately effective. There are no approved medications for CUD, thus identifying novel pharmacotherapies for this disorder is an important unmet need. The long-term goal of this project is to bring to market a safe and effective pharmaceutical drug treatment that leverages novel mechanisms of action to reduce cocaine use and improve abstinence. We have discovered two molecules featuring different mechanisms of action that may plausibly be effective in treating CUD. The current project will evaluate these two compounds for their effects in behavioral models evaluating cocaine- and non-drug-related reinforcement, and stress-induced reinstatement of drug-seeking behavior. Specifically, we will evaluate the ability of these two molecules to reduce the number of cocaine infusions in cocaine self-administration studies based on a fixed ratio schedule of reinforcement. We will then evaluate the most effective molecule in a stress-induced reinstatement assay, which evaluates the ability of the compound to prevent a relapse induced by stress after a drug-free period. If our compound is effective with a single dose, we will examine whether it remains effective at suppressing stress-induced reinstatement after repeated administration. Finally, we will evaluate whether the effects of the compound also modify the reinforcing value of food in a fixed ratio schedule of reinforcement. The resulting data will help us understand to what extent the effects of the compound are selective for drug and non-drug reinforcers.