Brain’s sensory regions play a role in fentanyl relapse



The relapse rate for people addicted to opioid drugs is remarkably high and contributes greatly to the U.S. opioid crisis. Addiction relapse in animal models has been extensively studied in the lab, where drug use is carefully controlled; however, outside the lab, a person’s decision to stop using a drug is up to the user, since the drug may still be available. Additionally, the opioid overdose crisis is driven in large part by the potent synthetic opioid fentanyl, but few preclinical studies have investigated the processes at work in the brain that lead to addiction relapse when fentanyl is involved.


IRP researchers led by David Reiner, Ph.D., a postdoctoral fellow in the lab of Yavin Shaham, Ph.D., studied fentanyl relapse in rats who were trained to self-administer both food they particularly liked and intravenous doses of fentanyl. After two weeks of choosing food over fentanyl, the animals subsequently resumed using fentanyl when they no longer had access to their preferred food, a situation resembling drug relapse in humans. The experiment revealed a novel role for a part of the brain involved in the sense of smell, called the piriform cortex, in fentanyl use relapse after a period of voluntary abstinence. The research also revealed that neural connections extending from the piriform cortex to the orbitofrontal cortex, a region associated with decision-making and heroin relapse, are critical for fentanyl relapse.


These unexpected results illustrate an underappreciated role for sensory-related brain regions, such as the piriform cortex, in fentanyl relapse. Understanding the brain processes involved in fentanyl relapse may lead to the development of new treatment strategies for opioid addiction and overdose prevention. Additionally, these findings support the notion that the brain systems involved in relapse are similar across opioid drugs, which may be important for the implementation of medication-assisted and behavioral treatments for opioid addiction.


Reiner DJ, Lofaro OM, Applebey SV, Korah H, Venniro M, Cifani C, Bossert JM, Shaham Y. (2020). Role of projections between piriform cortex and orbitofrontal cortex in relapse to fentanyl seeking after palatable food choice-induced voluntary abstinence. J Neuroscience. Mar 18;40(12):2485-2497.

View All Health Topics

This page was last updated on Thursday, June 8, 2023