Description du projet
Des thérapies de la toxicomanie fondées sur des données probantes
La toxicomanie fait payer un lourd tribut à la société, son emprise neuropathologique omniprésente entraînant des coûts personnels et sociétaux dévastateurs. Le cœur de ce formidable défi réside dans la tendance persistante aux récidives, en particulier dans les environnements associés à la consommation de drogues. Dans cette optique, le projet DrugsAndMemory, financé par le CER entend révolutionner notre compréhension et notre gestion de la dépendance. En démêlant les circuits neuronaux complexes qui relient les motivations à la consommation de drogues aux facettes spatiales et non spatiales des contextes associés aux drogues, ce projet devrait mener à des découvertes révolutionnaires cruciales susceptibles de prévenir et inverser les comportements d’addiction aux drogues déclenchée par le contexte. En utilisant des techniques de pointe, notamment des enregistrements in vivo et l’optogénétique, le projet décode l’interaction complexe des indices spatiaux et non spatiaux qui déterminent le comportement d’addiction aux drogues.
Objectif
Addiction to drugs is a ubiquitous neuropathological disease that inflicts immense societal costs. A core aspect of addiction that poses a major challenge for treatment is the propensity to relapse in environmental contexts that are associated with drug use. Identification and mechanistic characterization of novel addiction-relevant circuitry linking the motivation to take drugs to the complex spatial and non-spatial features that constitute a drug-associated context are at the core of this proposal. These insights will be used to identify the best constellation of anatomical targets to prevent and reverse the expression of context-triggered drug-seeking. The medial and lateral entorhinal cortex (MEC and LEC) are two central components of the episodic memory system integrating all features relevant for the formation of contextual memory. Crucially, MEC and LEC receive strong bottom-up dopaminergic input from the midbrain and send top-down projections to the nucleus accumbens (NAc). The dopaminergic system is the primary target of all addictive drugs. We will 1) study how bottom-up dopaminergic projections are implemented into drug-context associations in MEC and LEC and 2) determine how these associations influence NAc-mediated drug-seeking behaviour. We will utilize a multidisciplinary approach by developing electrophysiological in vivo recording paradigms in behaving mice that allow the assessment of complex spatial, contextual and non-spatial codes in conditioned place preference and self-administration paradigms typically used to model addiction in rodents. This will be combined with optogenetically-assisted circuit analysis of molecularly-defined pathways to link identified functions to the underlying circuitry. Pathway-specific optogenetic silencing will be used to prevent and reverse the manifestations of drug use on a neuronal and behavioural level. This will guide the evidence-based development of therapies in the future, such as deep-brain stimulation.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Thème(s)
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
69120 Heidelberg
Allemagne