Project description
Understanding the neural basis of fentanyl addiction
Fentanyl is a powerful synthetic opioid analgesic used to treat patients with severe pain. More than a third of users eventually become addicted, a number that is significantly higher than that observed with psychostimulants; consequently, there is an increased risk of death by overdose. The EU-funded F-Addict project aims to uncover the neural basis of fentanyl addiction, understand the molecular mechanism of circuit modulation and define future therapies in the face of the growing opioid overdose epidemic. It will study the synaptic processes and neuronal population activity leading to addiction using a mouse model of oral fentanyl self-administration. The project will define the role of positive and negative reinforcement in fentanyl addiction in contrast with current circuit models based on psychostimulants.
Objective
F-Addict strives to unravel the neural circuits driving compulsion in fentanyl addiction. We ask the question how fentanyl causes fast transition from medical or recreational controlled drug use to compulsive consumption. About a third of opioid users eventually loose control, which increases the risk of death by overdose; a number that is even higher for fentanyl and definitely exceeds the transition observed with psychostimulants. The neural correlate of this difference remains elusive. We posit that repetitive withdrawal leads to strong negative reinforcement, which in conjunction with inherent positive reinforcement favors the transition to compulsion. F-Addict will uncover the synaptic processes and neuronal population activity leading to addiction in a mouse model of oral fentanyl self-administration. Much preliminary data implicate activity in the mesolimbic dopamine system and upstream subcortical regions (paraventricular thalamus/habenula/basolateral amygdala) in positive and negative reinforcement, respectively. In addition, top down control, in particular by the orbitofrontal cortex may drive compulsive drug use. The proposed project will harness advanced circuit investigations for an innovative, original perspective: how does positive and negative reinforcement in fentanyl addiction contrast with current circuit models of addiction that are based on psychostimulants? In a translational spirit, F-Addict will also examine the effects of oral substitution with methadone and buprenorphine, recognized therapies for opioid addiction. Much preliminary data provides proof of feasibility and principle. We are confident that our approach at the frontiers of modern neurosciences carries the potential for groundbreaking results to answer a timely question. Unraveling the neural basis of fentanyl addiction will enhance the molecular understanding of circuit modulation to shape future therapies facing the still growing opioid epidemic.
Fields of science (EuroSciVoc)
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CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
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Programme(s)
Topic(s)
Funding Scheme
ERC-ADG - Advanced GrantHost institution
1211 Geneve
Switzerland