The Serotonin 5-HT2AR, a Novel Non-Opioid Target for Opioid Use Disorder

Led by Erik Garcia

University of Nebraska Omaha

Study Overview:

This project seeks to uncover a non-opioid target that is 1) functionally unaffected by chronic administration of oxycodone and 2) able to reduce the reinforcing value of oxycodone. Together these properties would have the capability to decrease the abuse potential of prescription opioids.

Specific Aims:

(Aim 1): Determine the functional status of the 5-HT2AR following oxycodone exposure.

(Aim 2): Uncover the efficacy of the 5-HT2AR to exert control of oxycodone reinforcement.

Study Sample Population:

These preclinical experiments will be conducted in male and female rats..

Unique Study Procedures:

This project utilizes strong behavioral neuropharmacology experiments to provide insights into the neural mechanisms of opioid reinforcement. Dr. Garcia will use statistical modeling and theoretical frameworks borrowed from behavioral economics to analyze the extent to which the 5-HT2AR modifies oxycodone consumption.

Long-Term Goals:

The long-term goal of this project is to develop a new class of selective and therapeutically useful 5-HT2AR small molecules for the treatment of opioid use and substance use disorders. The pilot grant will reveal the extent to which the 5-HT2AR reduces oxycodone reinforcement value. This project will have a lasting impact because prescription opioids are effective analgesics but have the potential for abuse. These experiments may reveal that 5-HT2AR drugs could be used to reduce the abuse potential of prescription opioid medications, making them safer for chronic use.

Erik Garcia

Project Director

In Fall 2021, Dr. Garcia started his career as Assistant Professor of Neuroscience and Behavior at the University of Nebraska Omaha. He researches the neurobiological mechanisms that dictate the consumption of rewards and reinforcers. After completing his doctoral degree in Experimental Psychology (Behavioral Neuroscience), he went to the University of Texas Medical Branch at Galveston to complete his postdoctoral training. There in the laboratory of Kathryn Cunningham, Ph.D., he researched serotonin and other G protein-coupled receptors families. Dr. Garcia helped reveal a novel series of 5-HT2CR and 5-HT2AR allosteric modulators that alter high-fat food consumption and cocaine and fentanyl relapse.

Full Erik Garcia bio