OPIOID: Fentanyl, a risk of cerebral and behavioral alteration?

Fentanyl, a mu-opioid receptor agonist, is one of the most commonly used analgesics in hospitals and can induce long-lasting behavioral and somatosensory impairment in rodents. It is not known, however, whether its use could promote the development of autism. This animal study by researchers from Massachusetts General Hospital (MGH), Shanghai 10th People’s Hospital and the University of Pennsylvania reveals that fentanyl can induce changes similar to autism-like behaviors in young male and female mice.

A result that should alert but not lead to avoid the use of fentanyl in the hospital

Previous research has suggested that dysfunction of N-methyl-D-aspartate receptors contributes to autism. Variations in Grin2a and Grin2b, the genes encoding the GluN2A and GluN2B subunits of the N-methyl-D-aspartate receptor, are associated with autism. Additionally, the anterior cingulate cortex of the brain is affected in autism. The team shows here, in mice exposed to fentanyl, the involvement, and specifically the reduction in the expression of Grin2b induced by hypermethylation in the anterior cingulate cortex.

“The anterior cingulate cortex is a hub for mediating social information, so we focused on the expression of Grin2b in this brain region,” explains lead author Dr. Yuan Shen, professor of psychiatry at Shanghai. 10th People’s Hospital: “We find that fentanyl decreases Grin2b expression in the anterior cingulate cortex. In contrast, overexpression of Grin2b prevents fentanyl-induced autistic-like behavior in mice. These results suggest

a possible mechanism, to explain or prevent drug-induced autistic-like behavior”

These results need to be validated in humans, especially because the changes seen in mice in behavioral tests do not correlate with autism in humans. These behavioral tests are only used to study autism-like behaviors in mice because they can demonstrate certain characteristics of behavioral changes similar to the manifestation of autism in humans, the researchers say.

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Thus this animal study result should alert but is in no way an indication to avoid fentanyl in clinical anesthesia. However, it should encourage further research, including clinical investigations, to determine the potential neurobehavioral influence of opioids on brain development.

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