Study finds fentanyl, an opioid pain reliever, can cause autism-like behavior in young mice

Fentanyl, a myo-opioid receptor agonist, is one of the most widely used analgesics in the hospital and can cause long-term behavioral and sensory impairment in rodents. However, it is not known if fentanyl use is associated with the development of autism. An animal study conducted by researchers at Massachusetts General Hospital (MGH), Shanghai 10e People’s Hospital and the University of Pennsylvania have shown that fentanyl can induce changes similar to autism-like behavior in young male and female mice. The conclusions are published in British Journal of Anesthesia.

Research by other groups has shown that dysfunction of the N-methyl-D-aspartate receptor contributes to autism. variables in Grin2a And the Grin2b, genes encoding the GluN2A and GluN2B subunits of the N-methyl-D-aspartate receptor, are associated with autism. In addition, the brain’s anterior cingulate cortex is affected by autism.

In this current study, the research team reports that fentanyl induces autism-like behaviors in young male and female mice by activating myo-opioid receptors in the anterior cingulate cortex. Furthermore, these fentanyl-induced autism-like behaviors appear to be due in part to a reduction in hypermethylation mediated by Grin2b Expression in the anterior cingulate cortex of rats.

“Because the anterior cingulate cortex is a center for mediating social information, we focused on the expression of Grin2b in this area,” says Yuan Shen, MD, PhD, lead author of the paper and professor of psychiatry at Shanghai 10e People’s Hospital. We found that fentanyl reduces expression Grin2b in the anterior cingulate cortex. overexpression Grin2b Inhibits autism-like behavior induced by fentanyl in mice. These findings suggest a potential mechanism for preventing or treating autism-like behavior,” says Shen.

The group conducted experiments using the open field test (in which a mouse can walk inside a box) and an elevated maze (in which a mouse can walk on an elevated platform) to detect anxiety and stereotypical behaviors of the mice. Using a three-chamber social preference test (in which a mouse can interact with another mouse), they also assessed potential social deficits. “We used these tests because impaired social interaction, stereotyped behaviors, and anxiety are the main hallmarks of autism-like behaviors in mice,” says Zhihao Sheng, co-first author of the paper. Sheng is a graduate student in Shanghai 10e People’s Hospital.

“However, mice changes in these behavioral tests are not associated with autism in humans. These behavioral tests are only used to study autism-like behaviors in mice because they can show certain characteristics of autism-like behavioral changes,” said Qidong Liu, Ph.D., first author Associate and Assistant Professor in Shanghai 10e People’s Hospital.

Co-lead author Zhongcong Xie, MD, PhD, adds, “There is no current evidence that fentanyl is associated with a similar effect in humans and the animal study result is not indicative. To avoid fentanyl in clinical anaesthesia. The finding will advance further research, including that clinical investigations, to determine the potential neurobehavioral effect of opioids on brain development.Xie is director of basic science research in the Division of Anesthesia, Intensive Care, and Pain Medicine at MGH and Henry K. Beecher Professor of Anesthesia at Harvard Medical School.

Other authors are Chun Cheng and Mengzhu Li from Shanghai 10e People’s Hospital and Shanghai First Maternity and Children’s Hospital, W. Andrew Koffke of the University of Pennsylvania and Jed Barash, MD, a neurologist from Massachusetts.

This research was supported by the Ministry of Science and Technology of China and the National Natural Science Foundation of China.

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