The double face of fentanyl: the neuronal basis of opioid addiction
…fentanyl… triggers the activation of the dopamine neurons in the mesolimbic system (also known as the reward system), which includes the ventral tegmental area and the nucleus accubens. The neurons then release a large quantity of dopamine. Normally, dopamine neurons are under the control of inhibitory GABA cells. However, opioids block GABA neurons, which makes dopamine neurons more active, inducing a euphoric phase. The key to understanding is the mu opiate receptor.
Until now, it was thought that the mechanisms of both positive and negative reinforcements takes place in the same brain area, the mesolimbic system. Conversely, [the team’s] hypothesis suggests that the origin of negative reinforcement is to be found in cells that express the mu receptor elsewhere in the brain, explains Fabrice Chaudun, postdoctoral fellow in Christian Lüscher’s laboratory and first author of this work. The scientists used a series of behavioural and neuronal observation experiments to test their hypothesis. The first step was to suppress the mu receptor in the ventral tegmental area of mice addicted to fentanyl. If positive reinforcement disappeared, withdrawal remained unchanged. By reproducing the experiment in different neuronal networks, [the team] managed to identify a population of as yet unknown cells that express the mu receptor in another brain region, the central amygdala, known to be linked to fear and anxiety», says Fabrice Chaudun. By suppressing the mu receptor in the cells found there, withdrawal symptoms disappear, but positive reinforcement does not.
Original Article (University of Geneva):
The double face of fentanyl: the neuronal basis of opioid addiction
Artwork Fair Use: Dr Bruno Di Muzio
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