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.
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