Research Wire

$3.4 million grant aims to study how fentanyl disrupts the brain’s locus coeruleus system

The National Institute on Drug Abuse (NIDA) has awarded Jordan McCall, PhD, an associate professor in the Center for Clinical Pharmacology in the WashU Medicine Department of Anesthesiology, a five-year, $3.4 million grant to study how fentanyl disrupts the brain’s main alert and stress center — the locus coeruleus — and drives relapse to opioid use.

Jordan McCall, PhD; Ream Al-Hasani, PhD; Jose Moron-Concepcion, PhD
From left: Jordan McCall, PhD; Ream Al-Hasani, PhD; Jose Moron-Concepcion, PhD

The locus coeruleus is a source of the brain’s natural pain relief, but growing evidence suggests chronic opioid exposure can transform it into a driver of drug seeking and negative mood. McCall’s team has found that neurons in the locus coeruleus have a natural “off switch” — receptors that respond to the body’s own opioids — which normally keeps drug reward in check. When that off switch weakens, it may make relapse more likely. In collaboration with the Al-Hasani lab and Moron-Concepcion lab, the McCall lab will examine how this loss of natural inhibition after long-term fentanyl use affects brain circuits tied to negative mood and cravings. 

Read more on the Department of Anesthesiology website.