Clarifies fentanyl mechanisms to create dependency

2024/05/28 Galarraga Aiestaran, Ana - Elhuyar Zientzia Iturria: Elhuyar aldizkaria

with mice show that fentanyl exerts dependence through two brain mechanisms, and that the sum of both causes dependence or addiction to be so large. One mechanism is the prize circuit (positive reinforcement) and the other is the one that seeks to avoid withdrawal syndrome (negative reinforcement). The neural networks and receptors involved in these mechanisms have been identified and the results published in the journal Nature.

Mouse brain in 3D. Ed. Allen/CC 4.0 Institute

Like heroin and morphine, fentanyl binds to opioid receptors and causes dopamine secretion. It produces pleasure, analgesia and loss of consciousness. If continued use causes tolerance (higher doses are needed to achieve the same effect) and withdrawal symptoms. Its strong impact provokes a strong addiction that has become a serious health crisis, especially in the United States.

To better understand the mechanisms that cause addiction, the authors of the article have conducted experiments with mice. So they first got fentanyl and they saw that fentanyl acts on the ventral tegmental area of the brain (VTA): it deinhibits dopamine neurons and releases dopamine into the nucleus accumbens. If ATV opioid receptors are inactivated, they observed that dopamine emission is interrupted and the positive effect is reversed, but the withdrawal syndrome does not disappear.

Thus, in the next step, researchers identified activated opioid receptor neurons in withdrawal syndrome in the central amygdala area (CeA). The deactivation of these receptors made the withdrawal symptoms disappear. They have shown themselves to be responsible for negative reinforcement. These results have been confirmed by optogenetics.

Researchers hope that research will pave the way for research into these mechanisms in humans as well and help reduce addiction and facilitate rehabilitation.


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