You are here : Home > News > Better understanding opioid tolerance through brain imaging

Scientific result | Article | Positron Emission Tomography | Molecular mechanisms

Better understanding opioid tolerance through brain imaging


A study combining PET imaging and pharmacology, conducted by researchers at BioMaps (SHFJ), suggests that decreased availability of opioid receptors and altered neuronal energy metabolism constitute molecular signatures of opioid tolerance. These observations, made in an animal model, could help improve understanding and treatment of opioid dependence.

Published on 6 August 2025

The misuse and addiction to opioids, such as morphine, represent a major public health issue. The phenomenon of tolerance—i.e., the reduced sensitivity to the effects of opioids associated with prolonged use—is considered a key risk factor, notably for overdose. What are the molecular and cellular mechanisms underlying tolerance? Traditionally, it is thought to be linked to reduced availability of mu opioid receptors and to disruptions in the opioid signaling pathway affecting the coupling between mu receptors and their effectors.​

Can these molecular determinants be accounted for? 

Researchers from the Neuropharmacological Imaging team at BioMaps (SHFJ) developed an animal (rodent) model of morphine tolerance, induced by several days of morphine administration followed by withdrawal, and performed two types of imaging tests:

  • A PET scan coupled with a pharmacological competition between buprenorphine, a morphine agonist at mu receptors, and its carbon-11–labeled analogue. Using this test — developed and validated by the team (see 2021 publication, PET imaging reveals the neuropharmacology of buprenorphine) — the researchers showed a reduction in the number of available mu opioid receptors in certain brain regions ​of tolerant animals comparend with controls. 
  • A fluorine-18-labeled FDG PET scan that revealed alterations in cerebral glucose metabolism in tolerant animals. 

Their approach enables the detection and quantification of these changes, making them potential biomarkers of tolerance. It could therefore provide a means to better diagnose, monitor, and treat opioid tolerance in humans.

Cont​​​act at Frédéric-Joliot Institute for Life Sciences:

Nicolas ​Tournier (nicolas.tournier@cea.fr)

Top page