Fentanyl can cause autism-like behavior in young mice

Overview: Exposure to opioid fentanyl induces autism-like behavior in mice by activating opioid receptors in the anterior cingulate cortex.

sauce: Massachusetts General Hospital

Fentanyl, a muopioid receptor agonist, is one of the most commonly used analgesics in hospitals and can cause long-term behavioral and somatosensory disorders in rodents. However, it is unclear whether the use of fentanyl is associated with the development of autism.

Animal studies led by researchers at Massachusetts General Hospital (MGH), Shanghai 10th People’s Hospital, and University of Pennsylvania show that fentanil can cause autism-like behavior in young male and female mice. It has been.

The survey results are British Journal of Anesthesia Science..

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

In this current study, the researchers report that fentanyl induces autism-like behavior in young male and female mice by activating muopioid receptors in the anterior cingulate cortex. Moreover, these fentanyl-induced autism-like behaviors are partly due to hypomethylation-mediated reduction in Grin2b expression in the anterior cingulate cortex of mice.

“Because the anterior cingulate cortex is a hub that mediates social information, we focused on the expression of Grin2b in that area,” said Yuan, lead author of the paper and professor of Shanghai 10th People’s Psychiatry. Shen, MD, Ph.D. states. hospital.

“We found that fentanyl reduced Grin2b expression in the anterior cingulate cortex. Grin2b overexpression prevents fentanyl-induced autism-like behavior in mice. These findings are like autism. It suggests a potential mechanism for preventing or treating behavior, “Shen says.

This group conducted experiments using an open field test (mouse can walk in a box) and an elevated cross labyrinth (mouse can walk on an elevated platform), and mouse anxiety and stereo. Detected a type of behavior. A three-chamber social preference test (where one mouse can interact with another mouse) was also used to assess potential social defects.

“We used these tests because impaired social interaction, stereotypical behavior, and anxiety are important features of behavior such as autism in mice,” said Zhihao Sheng, co-lead author of the paper. Says. Shen is a graduate student at Shanghai 10th People’s Hospital.

“But the changes in mice in these behavioral tests are not the same as in human autism, because these behavioral tests can show certain characteristics of behavioral changes similar to the symptoms of autism. It is only used to study autism-like behavior in mice, “said Dr. Qidong Liu, co-lead author and assistant professor. Shanghai 10th People’s Hospital.

Co-author Zhongcong Xie, MD, Ph.D. adds:

“But the results will facilitate further research, including clinical research, to determine the potential neurobehavioral effects of opioids on brain development.”

Xie is Director of Basic Science Research in MGH Anesthesiology, Critical Care and Pain Medicine, and Professor of Anesthesiology Henry K. Beecher, Harvard Medical School.

Other authors include Chun Cheng and Mengzhu Li of Shanghai 10th People’s Hospital and Shanghai 1st Obstetrics and Gynecology Hospital, W. Andrew Kofke of the University of Pennsylvania, and Jed Barash, a neurologist in Massachusetts.

See also

About this neuropharmacology and ASD research news

author: Michael Morrison
sauce: Massachusetts General Hospital
contact: Michael Morrison – Massachusetts General Hospital
image: The image is in the public domain

Independent research: Closed access.
“”Fentanyl induces autism-like behavior in mice by hypermethylating the glutamate receptor gene Grin2b“Zhihao Shengetal. British Journal of Anesthesia Science

Overview

Fentanyl induces autism-like behavior in mice by hypermethylating the glutamate receptor gene Grin2b

Background

Environmental factors contribute to autism spectrum disorders. Fentanyl, one of the most widely used opioid analgesics in anesthesia, can induce neurotoxicity, but its role in autism remains unclear. We determined whether fentanyl induced autism-like behavior in young mice and the underlying mechanism.

Method

Young male and female mice were treated with fentanyl on days 6, 8 and 10 years of age, including 3 chamber social preferences, elevated cross maze, grooming behavior, and open field studies from 30 to 32 days of age. We conducted a behavioral test.Expression Grin2b, Gene encoding the GluN2B subunit of N-Methyl-d-aspartate receptor was assessed in the anterior cingulate cortex of male mice using fluorescence there Hybridization histochemistry.Determined using bisulfite target sequence Grin2b Hypermethylated sites after fentanyl treatment.In certain activation and rescue experiments, muopioid receptor agonists were injected. [D-Ala,² N-MePhe,⁴ Gly-ol]-Enkephalin (DAMGO) or Grin2b Overexpression of lentivirus in the anterior cingulate cortex of male mice.

result

Fentanyl induced autism-like behavior in both young male and female mice and was downregulated. Grin2b Equation (0.49 times [0.08] vs 1.00 times [0.09]; P<0.01) and the amount of GluN2B protein (0.38 times) [0.07] vs 1.00 times [0.12]; P<0.01) Due to hypermethylation of the anterior cingulate cortex Grin2b..With the muopioid receptor antagonist naloxone Grin2b DAMGO injection into the anterior cingulate cortex induced autism-like behavior, whereas the fentanyl-inducing effect was diminished in the anterior cingulate cortex.

Conclusion

These data suggest that fentanyl induces autism-like behavior in young mice through epigenetic mechanisms. Further research is needed to determine its clinical relevance to the risk of autism.