Ryan Murphy
Testing a New Therapeutic Approach for Treating Stimulant Dependence
Summary
Misuse and abuse of stimulants such as cocaine and amphetamines is a pervasive health concern affecting over 10 million Americans. Chronic stimulant use disrupts normal circuitry in the brain, impairing daily life and commonly leading to physical and psychological dependence. Unfortunately, there are no existing drug therapies to treat stimulant dependence or abuse. My project features a new potential drug target, a receptor protein called GPR52, which acts oppositely to stimulants in the brain circuitry that controls the sensations of reward and motivation. My lab recently discovered a unique molecule that activates GPR52 and may reverse stimulant-induced brain dysfunctions. Using a combination of techniques in human cell lines and computational models, I will profile the activity of newly designed variations of this molecule on several GPR52 cellular signaling pathways. With these data, I will select the most effective and drug-like GPR52 activator, which will then be tested for reducing cocaine-taking and cocaine-seeking behaviors in rodent models. My goal is to advance our basic understanding of the GPR52 receptor protein and validate GPR52 as a therapeutic target for treating stimulant abuse and dependence.
This award from the PhRMA Foundation has provided me more independence and support to pursue innovative research in neuropharmacology. The funding will allow me to further my training using new techniques and integrating drug discovery with translationally relevant models of stimulant abuse. The skills I gain from this project will push me to become a more successful researcher, while the pharmacological insights we gain will help to advance our understanding of substance use disorders and the therapeutic potential for modulating activity of orphan G protein-coupled receptors, like GPR52.
