Fentanyl, a mu-opioid receptor agonist, is one of the most commonly used analgesics in hospital settings and can cause long-lasting behavioral and somatosensory impairments in rodents. However, it is not known whether 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 will be published in British Journal of Anesthesia.
Research from other groups has shown that dysfunction of N-methyl-D-aspartate receptors contributes to autism. variants one Grin2a and grin2b, the genes encoding the GluN2A and GluN2B subunits of the N-methyl-D-aspartate receptor are implicated in autism. In addition, the anterior cingulate cortex of the brain is affected in autism.
In this recent study, the research team reported that fentanyl induces autistic behaviors in young male and female mice by activating the mu-opioid receptor in the anterior cingulate cortex. Furthermore, these fentanyl-induced autistic-like behaviors appear to be due in part to the hypermethylation-mediated reduction of grin2b Expression in mouse anterior cingulate cortex.
“Since the anterior cingulate cortex is a hub for mediating social information, we focused on the expression of grin2b in this field,” said Yuan Shen, MD, PhD, lead author of the paper and Professor of Psychiatry at Shanghai 10e People’s Hospital. “We found that fentanyl decreased the expression of grin2b in the anterior cingulate cortex. The overexpression of grin2b prevents fentanyl-induced autistic behavior in mice. These results suggest a potential mechanism to prevent or treat autism-like behavior,” says Shen.
The group conducted experiments using an open field test (where a mouse can walk in a box) and an elevated maze (where a mouse can walk on a raised platform) to detect fear and stereotypical behavior in mice. They also assessed potential social deficits using a three-chamber social preference test (where one mouse can interact with another mouse). “We used these tests because impaired social interaction, stereotyped behavior, and anxiety are the main features of autism-like behaviors in mice,” says Zhihao Sheng, co-first author of the study. Sheng is a graduate student in Shanghai 10e People’s Hospital.
“However, mouse changes in these 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 show certain features of behavioral changes that resemble the manifestation of autism,” says Qidong Liu, PhD, co-first author and assistant professor at the Shanghai 10e People’s Hospital.
Co-lead author Zhongcong Xie, MD, PhD adds: “There is currently no evidence that fentanyl is associated with a similar effect in humans, and the outcome of the animal study is not indicative of avoiding fentanyl in clinical anesthesia.” The finding will stimulate further research, including clinical investigations, to determine the potential neurological impact of opioids on brain development. Xie is Director of Basic Research in the Department of Anesthesia, Critical Care and Pain Medicine at MGH and Henry K. Beecher Professor of Anesthesia at Harvard Medical School.
Other authors include Chun Cheng and Mengzhu Li of Shanghai 10e People’s Hospital and Shanghai First Maternity and Infant Hospital, W. Andrew Kofke of the University of Pennsylvania, and Jed Barash, a Massachusetts neurologist.
This research was supported by the Chinese Ministry of Science and Technology and the National Natural Science Foundation of China.
Source of the story:
Materials provided by Massachusetts General Hospital. Note: Content can be edited for style and length.