Objective
Individual vulnerability and resilience to drug addiction, resulting from gene-environment (GxE) interplay, remain poorly understood despite their profound implications for personalized interventions. Even with cocaine, a highly addictive drug, ‘only’ ~20% of human cocaine users will lose control and become addicted, a bimodal distribution also observed in rodents. In isogenic C57Bl/6 mice, it is again ~20% of the individuals that transition to addiction, suggesting a role for neuroepigenetic regulation of vulnerability and resilience. VARIANT will unravel the mechanisms underlying behavioral trajectories in addiction-like behaviors within genetically homogeneous mice, with a focus on neuroepigenetic mechanisms that modulate synaptic plasticity, shaping circuit function. Our preliminary data indicate that hallmark behavioral phenotypes—preference for drug over natural food reward, and measures of motivation and impulsivity—exhibit marked inter-individual variability.
VARIANT’s Aim1 will identify behavioral and epigenetic phenotypes predicting vulnerability and resilience for compulsive cocaine self-administration and in an optogenetic mimicry model of addiction. Aim2 will modulate the transition to compulsion through chronic mild stress exposure, while Aim3 will characterize the effects of stress exposure and environmental enrichment rescue on synaptic transmission in key addiction circuits. Aim4 will use behavioral and molecular interventions to ‘erase’ epigenetic changes and reduce addiction vulnerability, restoring resilience.
VARIANT will parse neuroepigenetic sources of variability, uncovering how life experience shapes the expression of identical genomes to yield divergent addiction trajectories. Our findings will inform personalized patient approaches by revealing behavioral and molecular vulnerability biomarkers, guiding circuit-level interventions to promote resilience. Ultimately, VARIANT will enable precision medicine in the field of addiction.
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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HORIZON.1.1 - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
HORIZON-ERC - HORIZON ERC Grants
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2025-ADG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
1202 Geneva
Switzerland
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.