Innovating Works

F-Addict

Financiado
Convergence of positive and negative reinforcement in fentanyl addiction
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... 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. ver más
31/05/2025
2M€
Duración del proyecto: 60 meses Fecha Inicio: 2020-05-13
Fecha Fin: 2025-05-31

Línea de financiación: concedida

El organismo H2020 notifico la concesión del proyecto el día 2020-05-13
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
ERC-2019-ADG: ERC Advanced Grant
Cerrada hace 5 años
Presupuesto El presupuesto total del proyecto asciende a 2M€
Líder del proyecto
UNIVERSITE DE GENEVE No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5