Two brain regions are activated by fentanyl

The addictive effects of fentanyl may be controlled by two different neural pathways in the brain, one involving reward and the other promoting the search for relief from withdrawal symptoms, according to a study in mice.

This breakthrough could help develop treatments to reduce addiction to this opioid, a powerful painkiller that is at the center of public health concerns in many countries such as the United States, according to EFE.

A combination of euphoric effects caused by the release of dopamine (positive reinforcement) and severe withdrawal symptoms (negative reinforcement) makes the drug addictive for around a quarter of users, according to a study in Nature.

A team led by the University of Geneva investigated the effects of fentanyl on the brains of mice, to which they administered the drug and induced withdrawal symptoms to identify the brain regions that are activated during positive and negative reinforcement.

Although it has been suggested that mu opioid receptors in the brain are related to this behavior, the neural circuits involved have not yet been precisely defined.

The researchers found that fentanyl induced activity in the ventral area of the brain, the region where dopamine is released. In addition, reducing mu opioid receptor activity in that area led to less dopamine release and fewer signs of positive reinforcement in the mice.

However, inhibiting the mu opioid receptor did not alter the withdrawal effects at all, suggesting that another pathway may be involved in mediating negative reinforcement.

The authors identified neurons in the central amygdala, another brain region, that also expressed mu opioid receptors and whose activity increased during withdrawal. Deactivating these receptors eliminated withdrawal symptoms in mice, suggesting that they play a role in mediating the negative reinforcement of fentanyl.

These findings could contribute to the development of interventions and medications to reduce fentanyl addiction and aid recovery, the authors propose.

In an accompanying article commenting on the study, Markus Heilig and Michele Petrella of Linköping University in Sweden said the findings “represent a major advance” in understanding how opioids promote addiction.

The authors of the commentary recall that in 2022, opioids accounted for about three-quarters of the 108,000 drug overdose-related deaths in the United States. EFE

Take a look

Deaths

In 2022, opioids accounted for about three-quarters of the 108,000 drug overdose-related deaths in the United States.

“Great advance”

Markus Heilig and Michele Petrella of Linköping University in Sweden, who wrote an article about the study, said the findings “represent a major advance in understanding how opioids promote addiction.”