Synthetic opioids like fentanyl are now the leading cause of fatal overdoses in the United States, but current treatments for addiction are hit-and-miss and often banned. , revealing neurological mechanisms that may lead to targeted and more effective medical responses.
Scientists at Texas A&M University School of Medicine have identified specific circuits in the striatum, the brain’s reward hub that controls voluntary movement and behavior. Many of the negative emotional states during fentanyl withdrawal arise from it and may even be the reason many chronic users relapse. After long periods of abstinence.
The study, co-authored by Jun Wang, an associate professor in the Department of Neuroscience and Experimental Therapies, suggests that inhibition of this particular circuit could significantly increase the chances of overcoming opioid drug disorders. increase.
Opioid addiction is primarily mediated by the mu opioid receptor (MOR) expressed on the direct pathway medium spiny neurons (dMSNs). These dMSNs facilitate drug-seeking behavior in users. It is located in the striatal patch subcompartment, where MOR-expressing dMSNs play a role in emotional processing and decision-making.
A study in mice examined how chronic exposure to opioids altered the activity of patch dMSNs. Scientists have found that fentanyl significantly enhances dMSN activity, and that during the early stages of withdrawal, inhibitory signals from dMSNs travel to dopaminergic neurons and are involved in motivating and rewarding behaviors and emotions. Did.
Wang and team noted that if these dMSNs could be inhibited, the subsequent negative emotional states associated with acute fentanyl withdrawal, such as anxiety and depression, could be mitigated and relapses less likely. bottom.
According to the National Institutes of Health, more than 80,000 deaths from opioid use will be recorded in the United States in 2021, largely due to synthetic opioids such as fentanyl. Fatal overdoses with these drugs increased by more than 7-fold from 2015 to 2021. Fentanyl is believed to be 50 times more potent than morphine.
As little is known about the neurological mechanisms of fentanyl addiction, this finding may be of importance for better drug-specific medical interventions to combat opioid use disorders.
The study was published in a journal cell report.
Source: Texas A&M University School of Medicine
